Pod Insights This Podcast Will Kill You Ep 204 Cancer Part 3: How do we treat it? About this episode A century and a half ago, the list of effective cancer treatments was essentially a single entry: surgery. Today, in 2026, you’d need pages to contain the number of treatments available, and multiple notebooks to delineate all of the various therapies currently in development. It is nothing short of a revolution. Of course, no revolution is perfect, and many cancer treatments are ineffective or carry risks of serious side effects. In part 3 of our cancer series, we delve into all facets of cancer treatment, from the history of their development to how they actually work. Tune in to learn how far we’ve come and where we might go from here in our perennial quest to treat and cure cancer.
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Transcript 16,962 words · 8 speakers
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0:06 Speaker 01 Hey folks, it's Matt Altmaix. And Joel Larsgaard. From the How To Money Podcast.
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2:08 Speaker 05 Throughout this series, we'll be discussing many aspects of cancer diagnosis and treatment, and we will be sharing several personal stories related to cancer. Some listeners might find this content upsetting. Please listen with discretion.
2:22 Speaker 06 Kia ora, my name is Amy and I'm a cancer survivor from Aotearoa, New Zealand. My family has a history with a type of cancer called retinoblastoma, which is a cancer of the eye. However, we can also track the history of how retinoblastoma is treated in New Zealand. Starting with my dad, he was diagnosed in 1956 with bilateral retinoblastoma, meaning he had it in both eyes. They treated him with radium, which looking back on it, obviously was not the most effective treatment. It didn't kill any of the cancer cells, but it also gave him myelodysplasia, a precursor to leukaemia. In the end, he had both his eyes removed so that the cancer wouldn't spread.
3:07 Speaker 06 I was diagnosed with bilateral retinoblastoma in 1994 and was given radiotherapy. Radiotherapy is quite good at killing the cancer cells, however, it also altered the shape of my skull and gave me other numerous side effects, which most of them were treated by either medication or surgery. In 2000, my sister Meg was diagnosed with trilateral retinoblastoma, meaning that she had the cancer in both of her eyes, but also a brain mass. She was treated with chemotherapy, which was still quite new at the time,
3:47 Speaker 06 and we thought that while at the time it was a very hard treatment, it was the best of the three. She had very limited side effects until she was 17 now. She was diagnosed with another form of cancer called osteosarcoma, not caused by the treatment, but a fairly common cancer to have with retinoblastoma as well. And she again was treated with chemotherapy. However, in the end, she got chemo-induced leukaemia, which is a very aggressive and rare form of cancer caused by the thing that was meant to save her life.
4:31 Speaker 06 Unfortunately, she passed away six weeks later. So here I sit, not being able to tell you if any treatment is amazing. But when you're faced with the alternative, you've got to go with what you've got. Thank you.
4:52 Speaker 07 Hi, my name is Hallie and I currently work as a nurse in the United States. I have experience in the operating room, endocrinology, and clinical trials. In each specialty, I've seen the effects of cancer in every aspect of one's life. It was only recently where I experienced cancer more personally as my dad was diagnosed in August of this year. I worked in oncology clinical trials from 2023 to 2025. For many of these studies, patients were only considered after failing a certain number of treatments. Essentially, they had to be sick enough but not too sick to qualify. For those patients who did consider being on study, I was amazed by the courage they had. Despite not knowing whether the treatment would ultimately heal or hurt them in the long run,
5:36 Speaker 07 they chose to proceed for the health of future patients who would inevitably come after them. In August 2025, my dad received the diagnosis of stage 2 oropharyngeal HPV-positive cancer at age 55. It was shocking to say the least. My experience with clinical trials prepared me to educate my family on what was happening and what would likely eventually happen based on the data gathered by past clinical trial participants. This knowledge gave my dad the confidence to share about his experience in our community. He completed treatment in November and has his follow-up pet in January, so fingers crossed for clear scans. I learned a couple of important things throughout these experiences. One is that cancer treatment and its side effects can be brutal.
6:21 Speaker 07 An oncologist I worked with once said, "The goal is to treat the patient. If treating the cancer gets in the way of that, we have to reevaluate the course of action." Number two is that cancer is not one size fits all. It can look like a chronic, slow-growing disease, and you can still live a very long, very happy, and very healthy life. It is not always a destination. Even if the disease is advanced, technology and medicine has come so far. Number three is that cancer is so common. Understanding that it's not if it infiltrates your life, but when it infiltrates your life is very important. This is very scary, I admit, but very comforting knowing you are not alone and knowing there are healthcare workers there, ready to fight the fight with you when the time comes, whether it's for you or a loved one.
7:52 Speaker 05 Thank you all so, so much for sharing your story with us. It truly means the world. Thank you to everyone who has written in. It, these stories add such, I mean, invaluable perspective on these stories of cancer and the experience with cancer. And we just really, really, really appreciate it.
8:12 Speaker 00 Yeah, we do. Thank you. We, we actually can't thank you enough for it. So, thank you. And we have a lot more stories that we'll be sharing throughout this series and throughout this episode today. Truly, thank you so much to everyone who submitted. We wish that we could have included all of your stories. They're, they all mean so much to us. So, thank you.
8:30 Speaker 05 They do. Hi, I'm Erin Welsh.
8:32 Speaker 00 And I'm Erin Omenupdike.
8:34 Speaker 05 And this is This Podcast Will Kill You.
8:36 Speaker 00 Welcome to episode three of cancer.
8:39 Speaker 05 Cancer, cancer. It's been a journey so far.
8:42 Speaker 00 I've learned a lot.
8:43 Speaker 05 Yes, same, same. This is three of four total episodes on cancer. If you haven't listened to the first two, you should definitely go check them out because they'll add, you don't have to.
8:55 Speaker 00 It's not like a requirement. Wired, but there's a lot of context there.
8:59 Speaker 05 Yeah, we recommend.
9:02 Speaker 00 We do.
9:02 Speaker 05 Strongly recommend.
9:03 Speaker 00 Yeah.
9:04 Speaker 05 And it's just to give you a little bit of sneak peek, if you haven't listened. Number one is all about what is cancer.
9:09 Speaker 00 What is it?
9:10 Speaker 05 Clinically, conceptually, how did we come by that knowledge throughout history? Episode two is about the evolution of cancer, the cellular basis of cancer.
9:18 Speaker 00 Why?
9:19 Speaker 05 What makes a cancer cell a cancer cell?
9:20 Speaker 00 Why do we get cancer?
9:22 Speaker 05 Why do we get cancer?
9:23 Speaker 00 Yeah.
9:23 Speaker 05 Cancer in animals, et cetera.
9:25 Speaker 00 Yeah.
9:26 Speaker 05 Today's episode is all about treatment.
9:28 Speaker 00 Treatment. Past, present, future?
9:30 Speaker 05 Yeah. That's, I mean, I think that pretty much sums it up.
9:33 Speaker 00 Yeah.
9:34 Speaker 05 And then next week, our final episode of the series, is all about sort of getting a sense of the current landscape of cancer around the world, in the US, and then some of the other strategies that we can use to try to drive down these numbers through screening and prevention.
9:50 Speaker 00 Prevention.
9:51 Speaker 05 Yeah.
9:52 Speaker 00 I love it. It's going to be great, and we've covered a lot already. We have a lot more to cover. But as much as we have packed into this series, there is a lot that we have not been able to fit.
10:04 Speaker 05 Yeah.
10:05 Speaker 00 So we want everyone to know that, number one, we have so many sources that everyone can read more about whatever your favorite aspect of the series has been.
10:14 Speaker 05 Right.
10:14 Speaker 00 There's more reading for you, so check out our website to see the list of sources. And these are not the only cancer episodes that we are ever going to do. We kind of think of this as like laying a baseline so that in future episodes, as we explore individual cancers, everyone's on the same page to start with.
10:30 Speaker 05 Mm-hmm.
10:31 Speaker 00 So.
10:32 Speaker 05 Be like, oh, so what's the difference between chemotherapy and surgery and radiation?
10:36 Speaker 00 You already know.
10:37 Speaker 05 Listen to this episode.
10:38 Speaker 00 Exactly.
10:39 Speaker 05 You know this.
10:40 Speaker 00 Exactly.
10:41 Speaker 05 Yeah, yeah. And as you'll hear throughout the series, as you've already heard, no two cancers or experiences with cancer are exactly alike.
10:47 Speaker 00 Yeah.
10:48 Speaker 05 And so, again, we just want to really express our gratitude to the firsthand account providers for giving us kind of a snapshot or a sneak peek into just some of the myriad ways that cancer can affect our lives, can affect, you know, the lives of people who have been diagnosed with cancer, who are undergoing cancer treatment, who have become unexpected caregivers, whose friends or loved ones are undergoing cancer treatment. It's, this is like... This is so important, especially because you and I talk about cancer from a biological perspective.
11:19 Speaker 00 Right.
11:20 Speaker 05 We're talking, I mean, a little bit of history, biology, evolution, but we're not talking about the experience as a cancer patient or somebody who has, you know, a loved one with cancer. And so, thank you.
11:29 Speaker 00 Thank you. We can't say thank you enough. Like, your firsthand accounts, I think, really make this series and make our podcast in general what it is. So, thank you.
11:39 Speaker 05 Truly, truly. Okay.
11:41 Speaker 00 Last piece of business.
11:43 Speaker 05 It is second to last. It is, I have an extra piece of business.
11:47 Speaker 00 Oh, yes, I forgot.
11:48 Speaker 05 Yeah, I can just, I'll do that business right now.
11:50 Speaker 00 Okay, okay, tell us.
11:51 Speaker 05 Before we do the final piece of business.
11:52 Speaker 00 I'm excited, so tell us, please.
11:53 Speaker 05 Sure, okay. So, I wanted to shout out a couple of episodes of Advances in Care. So, you know, in this series, in this podcast, We'll Kill You, we're doing cancer from like a very big-picture perspective. And so, if you want to get some nitty-gritty bits of information, there are a couple of episodes of Advances in Care that I want to shout out.
12:10 Speaker 00 This is the other podcast that Erin Welsh hosts.
12:12 Speaker 05 This is the other podcast I host, yeah, that features interviews with, and also just like experiences with physicians and physician scientists at New York Presbyterian. And so, there are some, just like such exciting research that's being done, and it's so cool to hear about it, like firsthand. So, there's an episode, episode 37, features Dr. Magna Trevetti, who's investigating chemotherapy-induced peripheral neuropathy and how to better understand it, which is such a significant aspect of like side effects of chemotherapy.
12:42 Speaker 00 It really is.
12:43 Speaker 05 So, really cool, important research. And then another one that's really recent, I believe it came out last week. Well, you know, it will come out in the future last week.
12:52 Speaker 00 Right, before, after this episode.
12:54 Speaker 05 Yeah. And it highlights work done by Dr. Scott Tagawa on the use of radioligand therapy in metastatic prostate cancer.
13:01 Speaker 00 Very cool.
13:02 Speaker 05 It's really cool stuff. I just didn't, I didn't even know about it, and I was like, this is the future.
13:06 Speaker 00 Yeah, 100%.
13:07 Speaker 05 That's, it's amazing. So, anyway, you can find Advances in Care wherever you get your podcasts.
13:12 Speaker 00 Yeah, check it out.
13:13 Speaker 05 Check it out.
13:14 Speaker 00 Okay, now, for actually the last piece of business, it's quarantine time.
13:18 Speaker 05 It's quarantine, it's placebo-ridden quarantine time.
13:20 Speaker 00 Exactly. We announced at the first episode of this series that we're not going to be putting alcohol in our quarantines anymore.
13:27 Speaker 05 Yeah.
13:28 Speaker 00 But it's a great name, so we're sticking with it. What are we drinking this week, Erin?
13:31 Speaker 05 Uh, the crab, the trappagato.
13:34 Speaker 05 Check out our social media to see me attempt to make it.
13:37 Speaker 00 Yeah, that's great. It'll be great. I think you'll be able to pull it off.
13:41 Speaker 05 Uh, we'll see. I could try. I could try. Also, check out our website, thispodcastwillkillyou.com for lots of cool things, transcripts, contact us form, firsthand account form, stuff like that.
13:51 Speaker 00 Yeah.
13:51 Speaker 05 Check it out.
13:52 Speaker 00 Merch, Patreon, et cetera. Rate, review, subscribe. We're on YouTube.
13:57 Speaker 05 Shall we? Done. Let's take a quick break and then
14:01 Speaker 00 Get into it.
14:02 Speaker 05 Get into it.
14:03 Speaker 00 Okay.
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14:48 Speaker 01 15 Sky Club visits plus four guest passes? That's up to $950,000 annual value. Value estimate based on a $50 per visit rate to purchase additional visits or bring a guest to the Delta Sky Club. It's the kind of premium access that helps you feel right at home and at ease no matter where you're headed. Apply today at www.delta.com/podcast. Offer ends November 4th, 2026. Minimum spending requirements and terms apply. This is Shirley Strawberry from the Steve Harvey Morning Show. Buy smart, drive for less, and trade for more. That's Toyota affordability. And it starts with a great deal on an all-wheel-drive Camry,
15:32 Speaker 01 Corolla Cross, or a Corolla Sedan with the latest features and tech. Or test drive a spacious Grand Highlander or adventure-ready RAV4. And with so many hybrid models Available, you can enjoy longer trips without all the stops. While Toyota's legendary resale value means you could get more at trade-in, get a great deal today and a great value tomorrow. Shop toyota.com for deals and details. Toyota, let's go places. Hello, hello, I'm Malcolm Gladwell, host of Smart Talks with IBM. Imagine your business depends on a system you didn't build and don't fully control. For years, it works perfectly. It's fast, reliable, affordable. So over time, more and more of your operations rely on it.
16:18 Speaker 01 Then one day, the terms change. What once felt flexible now feels difficult to leave. Moving to another provider or bringing those capabilities back under your own control could take years, cost millions, and disrupt the business in the process. That's the challenge of digital sovereignty. Businesses today rely on all sorts of third-party systems. Cloud platforms, data pipelines, AI models, software tools. Most days, these systems operate quietly in the background. But when something changes, like costs go up or rules shift, organizations are forced to confront how much control and flexibility they actually have.
17:02 Speaker 01 So to understand the challenge up close, I traveled to Paris to speak with IBM's Anupala Assis and Axas CIO, Giovanni Daniele, two people who think about these questions every day.
17:17 Speaker 01 Hear the full conversation at ibm.com/smarttalks or wherever you get your podcasts.
17:41 Speaker 01 On October 20th, 2024, I crossed the finish line at the Amsterdam Marathon, qualifying for both the Chicago and Boston Marathons. Six weeks later, I found a lump in my armpit. And two days after Christmas, I got the call. I had breast cancer. Looking back, I missed the warning signs. In August, I noticed a small cyst under my right nipple. I'd had cysts before, so I ignored it, waiting for it to go away. Later, my nipple started to flatten. That's a symptom I didn't recognize and I still didn't act. But when I found that lump, I called my doctor. The diagnosis: Stage 2 HR-positive, HER2-negative invasive ductal carcinoma. The most common type of breast cancer, except I'm a man, and that made it rare.
18:25 Speaker 01 My initial treatment plan was the standard: chemotherapy followed by surgery and radiation. But as a patient, I wanted to understand my options. The search for a second opinion led me to the Dana Farber Cancer Institute in Boston and their program for breast cancer in men. There, I joined the Ethan Clinical Trial, which replaced chemotherapy with endocrine therapy to study the efficacy of various drug combinations specifically for men. I became Ethan participant number nine, and that decision gave me clarity, direction, and purpose. I wasn't just benefiting from the research, I became the research. It turned my breast cancer nightmare into an adventure. And it gave me something else, too. It gave me the chance to live a normal life during treatment.
19:09 Speaker 01 Over the next nineteen weeks, I was treated with a combination of medications: an aromatase inhibitor, gonadal suppression, and a CDK4/6 inhibitor. And I kept running, even completing four marathons during treatment. That's something I would not have been able to do if I'd been on chemotherapy. My doctor's reactions were priceless when I told him about the races I'd run since our last visit. In June, I had a successful mastectomy and removal of six lymph nodes, and that was followed by radiation. As soon as I was cleared, I jumped back into marathon training. I had Chicago coming up in October and New York City in November, where I had a charity bib for the Breast Cancer Research Foundation. That's the organization that funded the Ethan Clinical Trial.
19:52 Speaker 01 And I'm all set to run Boston this April. Breast cancer in men is rare, roughly 1% of all breast cancer cases. Most men don't even know they can get it and wait too long to be checked. Awareness in male-specific research is needed to save these men's lives, like it's saving mine.
20:11 Speaker 01 My name is Charlotte Norup, and in September 2022, I was 41 years old, and I was diagnosed with stage 3 colon cancer. I had surgery to remove the cancer and 2 very large ovarian cysts, and my ovaries as well. And after that, I did 8 rounds of chemo and was told to consider myself cured. I would go in for a CT scan every year as a follow-up, and the first year, everything looked great. But in late 2024, the scan was showing some irregularities that needed additional scans, which led to a PET CT scan, and that came back with the result that my original colon cancer had metastasized to the top of my vagina
20:55 Speaker 01 and was spreading in my pelvis. In March 2025, I went in to have massive surgery to remove my bladder, my uterus, my rectum, some of my intestines, and appendix. And I woke up from surgery with a urostomy and a colostomy. I still have yet to accept either of these, and the urostomy has been difficult to deal with since we've discovered that I also have diabetes insipidus, which is a very bad combination with a urostomy.
21:27 Speaker 01 As I was recovering from surgery, I had a new CT scan for my lungs, which showed lots of nodules that they weren't able to diagnose at that point. These nodules turned out to be the original colon cancer that has metastasized to my lungs. This means that my cancer is now incurable, and I am going to die from this at some point.
22:14 Speaker 05 Last week, we looked at cancer through an evolutionary lens. Rather than seeing cancer as solely the enemy in an unrelenting war, we asked a different question: What does it mean to be a cancer cell? And why does it exist in the first place? That perspective shift allowed us to explore new ways to approach cancer treatment, not just by fighting evolution, but by working with it. And it helped us to better understand why many standard therapies may show initial promise, but then stop working for an individual. Over the past century and a half, cancer therapy has undergone a profound transformation, like truly hard to wrap your head around just how profound. Even in the last like 10 years.
22:59 Speaker 05 Yes. It's been amazing. Right. Yeah. But for for most of human history, cancer was rarely treated and never cured. Wow. Right? Yeah. Like that alone is monumental. Yeah. And in part, it's because it remained such a mystery to scientists and physicians. Treatment developments in the 20th century inspired initial hope that a cure for cancer, for all cancer, was possible. Yeah. After all, if we can put a man on the moon, why couldn't we cure cancer? Yeah. The answer is actually fairly straightforward. Besides the nature of cancer itself, which we learned about in episode one and episode two, the moon landing was guided by decades of foundational, basic research, whereas
23:42 Speaker 05 cancer research up through the 1970s had been centrally focused on treatment development without fully understanding the nature of cancer itself. The like underpinnings of that biology. Yeah. That makes sense. The genetics driving cancer, the different mutations, yeah, all these different things. All the things. The pathways. Yeah. And in fact, some early chemotherapy researchers actually disdained funding for basic research, seeing it as less urgent than devising treatments for the patients who were dying in front of them and they had seen dying over and over again. And you know, I think my initial reaction was like, basic research is the backbone to everything. Everything. It is how we understand the world, is you need basic research for application. 100%. Bottom line. Yeah.
24:25 Speaker 05 But I also do understand that frustration and that perspective and that impatience. Because, you know, if you think about it, these clinical oncologists were for years watching and their their patients die in front of them extremely limited.
24:40 Speaker 05 In their ability to do anything to save their patients or even just lessen their pain.
24:44 Speaker 00 And it is true that there are so many medicines that we use that we don't fully understand the mechanisms of how exactly they're working and they do a really good job.
24:53 Speaker 05 Right.
24:53 Speaker 00 And so, why do we need to do, I can understand.
24:56 Speaker 05 Totally.
24:57 Speaker 00 I don't feel it, but I understand that perspective.
25:00 Speaker 05 Absolutely, absolutely. I think that another aspect of this is that cancer, because of their limited ability to do anything, it challenges your role, your identity as healer.
25:09 Speaker 00 Yeah.
25:09 Speaker 05 If you go into medicine to save lives and you're faced with this thing that is not letting you do that, then it's like, I need to do something about this.
25:17 Speaker 00 Yeah.
25:17 Speaker 05 Right. But as the decades went on and as many new treatments failed to live up to initial expectations, it grew increasingly clear that if we wanted to understand why treatments failed or to devise improved treatments, basic research was absolutely necessary.
25:34 Speaker 00 Yeah.
25:34 Speaker 05 Yeah. So today, I'm going to tell the story of the three main treatment modalities that emerged over this period, prior to the extensive incorporation of basic research.
25:43 Speaker 00 Okay.
25:44 Speaker 05 And these are not the only ways that we treat cancer. I know that you're going to take us through many other really exciting therapies, but their development of these three has profoundly shaped the way that we think about cancer and how we continue our search for better therapies.
25:59 Speaker 00 Mm-hmm.
26:00 Speaker 05 Part one, surgery. From the earliest descriptions of cancer until the last years of the 19th century, the very last years, surgery represented the primary, if not the only, method of cancer therapy that showed any degree of success. But its popularity was uneven, and this is for good reason. Consider this 18th century, so 1700's description of mastectomies. This is pre-anesthesia, pre-antiseptic technique.
26:29 Speaker 00 I'm just like remembering the butchering art and like, it's not good.
26:33 Speaker 05 It's, that's his understatement.
26:35 Speaker 00 Yeah.
26:37 Speaker 05 Quote, "Many females can stand the operation with the greatest courage and without hardly moaning at all. Others, however, make such a clamor that they may dishearten even the most undaunted surgeon and hinder the operation. To perform the operation, the surgeon should be steadfast and not allow himself to become discomforted by the cries of the patient." End quote.
26:58 Speaker 00 Oh, man, oh, man, oh, man, oh, man, oh, man.
27:02 Speaker 05 Yeah. So rather than submitting themselves to that ordeal, many patients and physicians turned towards systemic treatments, which typically included a toxic chemical such as mercury, lead, or arsenic, which were our first chemotherapies, in a sense.
27:17 Speaker 00 Wow.
27:18 Speaker 05 You know, chemical cures or chemical treatments. Definitely not cures. When anesthesia and antiseptic technique came on the scene in 1846 and 1867, respectively, surgery transformed into a science. Surgeons could measure their progress. They could assess what worked and what didn't work. And as more and more cancer patients went under the knife and lived to tell about it, surgeons noticed that while many people recovered completely, in many more, the cancer recurred. It came back.
27:49 Speaker 00 Okay.
27:49 Speaker 05 The regrowth seemed concentrated on the margins of the original surgery. It was like tiny seeds of invisible cancer had just been left behind to then continue to grow. The answer to this problem seemed straightforward, right? Like, just cut away more during the initial surgery. With that, radical surgery was born.
28:10 Speaker 00 Okay.
28:11 Speaker 05 Surgeons in the late 19th and early 20th centuries pushed the metaphoric and literal borders of excision as far as they could. And most major solid tumors became fair game, even those that had previously been seen as too deep or too risky to attempt removal.
28:27 Speaker 00 Okay.
28:28 Speaker 05 Breast cancer, which had challenged every physician that attempted to treat it, became an early target of this radical approach, with many surgeons, notably William Halsted, advocating for wider and wider margins. First, the axillary lymph nodes, so the ones in your armpit, were removed. Then muscle, then maybe even bone. The question became, how much could we remove while still preserving life?
28:53 Speaker 00 Wow.
28:54 Speaker 05 Radical mastectomies may preserve life if you survived the initial surgery itself and the recovery period, but at what cost to quality of life?
29:03 Speaker 00 Right.
29:04 Speaker 05 That didn't seem to rank too highly for advocates of the radical approach, many of which who viewed a more conservative surgical approach as a quote-unquote "mistaken kindness." That's what it was often called, because it was like...
29:17 Speaker 00 You think you're being kind, but you're just leaving cancer behind.
29:21 Speaker 05 Exactly.
29:23 Speaker 05 Amid the early 20th century hype surrounding radical mastectomies, a few dissenting voices began to be heard. Their question was simple. Is that kindness always mistaken? As it turns out, no. The push towards radical mastectomies was initially spurred on by observations of tumor recurrence, and it was reinforced by armchair logic. It just seemed to make sense, right? You're like, of course, we want to cut more. Of course, we want to cut more. So it wasn't supported by statistical things, at least initially, that approach, the beginning of that approach. And to be fair, the state of breast cancer diagnosis during the late 1800s was nothing like it is today. There was no screening, so very early stages were unlikely to be detected,
30:08 Speaker 05 and diagnosis often followed clinical symptoms. So by the time that you actually went to the doctor to address something, you were like...
30:15 Speaker 00 It's already pretty far advanced.
30:17 Speaker 05 So, for example, in one case report, Halsted describes an eight-centimeter breast tumor as small.
30:23 Speaker 00 Oh, wow.
30:24 Speaker 05 So that is kind of like just shifting our perspective on what breast cancer...
30:29 Speaker 00 Right. Now, we're talking about like a matter of millimeters that you see on a mammogram that you would never be able to feel.
30:35 Speaker 05 Right. But eight centimeters being small.
30:38 Speaker 00 Wow.
30:39 Speaker 05 And the data backing up this approach is not entirely convincing, at least not for all cases. Three- or five-year survival rates varied drastically depending on how advanced the cancer was. Staging was an emerging tool at this time. And it left some people to question radical therapy as the universal approach that we should use for everything. So for localized, slow-growing tumors, a more radical approach resulted in greater tissue loss and disability than a more conservative surgery, which would have likely led to the same outcome, right? You didn't need to cut out as much as you did.
31:15 Speaker 00 That much, because this was slow-growing and wasn't going to cause those problems down the line.
31:19 Speaker 05 Right. But for those with more advanced cancer, radical mastectomies seemed unlikely to remove all cancerous tissue. It had already spread or metastasized. Right. And so it led one surgeon to conclude, quote, "Radical mastectomies' greater trauma is not justified by greater cure rates," end quote. We can make this surgery more and more painful, but it's not going to actually increase survival. But if a tumor was small at the time of surgery, and aggressive, and had not spread, yeah, a radical mastectomy might have been the way to go, might be the way to go. There was no one right answer. Yeah. And again, this like highlights this theme as cancer, of cancer being incredibly unique and requiring a personalized approach.
32:03 Speaker 05 But despite the mostly unconvincing data in support of radical mastectomies and the robust opposition to it, this approach dominated surgical treatment for breast cancer until the 1970s or so. Wow. Yeah, and in the 1980s also, but like it did fade over time. But then this was sort of more of the turning point where like a more balanced and personalized approach. Okay. Became, you know, the what to do. So, and there were, there were many things that changed this. The first was pushback from feminist groups who demanded that physicians consider the patient in these major treatment decisions. And the second was a large scale study published in the 1980s that compared survival, remission,
32:46 Speaker 05 and morbidity between radical and non-radical approaches that showed no difference in survival and remission, but greater morbidity with radical mastectomies. And then the third thing was that there were better advancements in cancer diagnosis. So like via X-ray and CT scans, and then also treatment, like radiation and chemotherapy had come onto the scene. Right. And so it was like, we can. We can do more. Do other things than a radical approach. Yeah. And so while for this surgical section, I focused mostly on breast cancer, surgery was an integral and often the only treatment for many types of cancers throughout the late 1800s, and a radical approach was justified in some cases more than others.
33:28 Speaker 05 Today, surgery remains a cornerstone of cancer treatment, along with radiation and chemotherapy. Part two. Part two. Radiation. Okay. Doing these in chronological order. I love this. Yeah. In the 1890s, around the same time that Halsted was spreading the word about radical mastectomies, two massive breakthroughs by three scientists were about to change the world forever. Okay. Like, not an exaggeration. The first, William Rontgen's discovery of X-rays in November 1895. Okay. And the second, Marie Sklodowska Curie and Pierre Curie's discovery of radium and polonium in 1898. Okay. It's amazing to me how those two things happened with just in a few years of each Like a couple of years apart. Yes.
34:13 Speaker 05 I know. And within a few years of these discoveries, physicians were utilizing radiation as a treatment for cancer.
34:21 Speaker 00 Really?
34:22 Speaker 05 Which is probably like the fastest turnaround time between initial discovery and application for anything ever.
34:28 Speaker 00 That's really wild. They were just like,
34:30 Speaker 05 everything.
34:31 Speaker 00 Wow, this thing, we can kill things with it.
34:33 Speaker 05 Yes, that's exactly what it was.
34:35 Speaker 00 Okay.
34:36 Speaker 05 Yeah, yeah. And these were not like the kinds of scientific discoveries. Like, I feel like we're so used on the podcast to being like, and then somebody discovered this and then it was rediscovered in this obscure journal years and years later.
34:49 Speaker 00 Yeah.
34:49 Speaker 05 No, it just instantly excited the broader scientific and medical community.
34:55 Speaker 00 Interesting.
34:55 Speaker 05 And there were, there was no shortage of people who were willing to work on X-rays and radium.
35:00 Speaker 00 Wow.
35:01 Speaker 05 Yep. And it didn't take long for these new radiation scientists to notice strange rashes after exposure to radiation, strange side effects, things like your hair would fall out, you would get these swollen skin, some kind of rash would emerge. Rather than evoking alarm, that alarm would come later, this led people to wonder whether radiation could be used to kill harmful tissue or cells, like cancerous tumors or bacteria. There's some controversy over who should hold the rightful title of first radiation therapist, which shows just how popular radiation therapy was in the early years, like, right after its discovery. But from my reading, the frontrunner appears,
35:45 Speaker 05 there are like multiple papers on this. The frontrunner appears to be a French physician, Victor Despignes.
35:52 Speaker 00 Okay.
35:53 Speaker 05 If that's, I don't know how you say his name. D E S P E I G N E S.
35:56 Speaker 00 Yeah, we tried to figure it out.
35:57 Speaker 05 Yeah, we were talking about it. Despignes' inspiration came from early reports demonstrating the bactericidal effects of X-rays. Guinea pigs inoculated with tuberculosis and then subsequently radiated did not develop the disease.
36:13 Speaker 00 Okay.
36:13 Speaker 05 Okay. So if you think back to the first episode in this series, cancer was commonly thought to be caused by pathogens
36:21 Speaker 00 Right, right.
36:22 Speaker 05 around this time. So, operating under this assumption, in July of 1896,
36:28 Speaker 05 Let me just remind you that
36:30 Speaker 00 X-rays nineteen eighty nine, eighteen ninety five.
36:32 Speaker 05 November eighteen ninety five.
36:34 Speaker 00 Wow.
36:35 Speaker 05 Wow.
36:35 Speaker 00 Less than a year.
36:36 Speaker 05 Yep. Despines used x-rays to treat a fifty-two-year-old patient of his who had stomach cancer.
36:41 Speaker 00 Wow.
36:42 Speaker 05 So he traced the outline of the tumor to, to track progress. At the end of treatment, Despines claimed improvement, not cure.
36:49 Speaker 00 Okay.
36:50 Speaker 05 But his conclusions have since been called into question. Whether he had success or not, he probably didn't. Whether his scientific reasoning was sound, it wasn't.
37:01 Speaker 00 Probably wasn't.
37:02 Speaker 05 Definitely wasn't.
37:05 Speaker 05 Victor, Victor Despines was likely the first person to apply radiation to a patient with the intention of shrinking a cancerous tumor.
37:12 Speaker 00 How interesting.
37:13 Speaker 05 Isn't that? Not Emil Grub, Grub, who was often claimed, even by me. I was like, wait a second, I didn't think it was this. I thought it was this other guy who did it. And I went back to our radiation notes from years ago.
37:25 Speaker 00 Right.
37:26 Speaker 05 And, um, no, well, hi, his story has been discarded because the first time he wrote about it was not at the time, but like thirty-something years later.
37:36 Speaker 00 Oh.
37:36 Speaker 05 He was like, oh yeah, that was me. I was the first. I did it because I had this idea.
37:40 Speaker 00 Okay.
37:41 Speaker 05 There's no like
37:42 Speaker 00 No actual record of it?
37:43 Speaker 05 Yeah.
37:44 Speaker 00 Okay.
37:44 Speaker 05 So, um, it doesn't matter. I like the, the reason I find this so interesting, this debate over priority, is because it shows just how excited people were about radiation.
37:54 Speaker 00 There were so many people.
37:55 Speaker 05 For many different things at the time. Yeah. Radiation, I mean, it was, it felt magical. It was science made magic, right? It allowed you to peer inside the body without using a knife. It made things glow in the dark. It emitted heat. It killed bacteria. What couldn't this precious substance do? Over the late eighteen hundreds and early nineteen hundreds, lab-based empirical science had established itself as the standard for developing and testing new treatments. So there was this increasing pressure to demonstrate the efficacy and safety, to a lesser degree, of a drug before administering it.
38:32 Speaker 00 Okay.
38:33 Speaker 05 For some physicians, this was an unwelcome affront that challenged or undermined the traditional role of doctor as healer. Like, what are you doing? Right? If treatments were being developed and tested by scientists in labs and then given to physicians to administer, didn't that just make physicians glorified drug dispensers? What were they actually doing then if they weren't testing out therapies on their patients?
38:58 Speaker 00 So interesting, Erin.
38:59 Speaker 05 Yeah. I mean, also, painting with a broad brush, et cetera. But I do think that there was initial pushback against this, the science in medicine and like using statistics rather than experience.
39:11 Speaker 00 Okay.
39:11 Speaker 05 You know? And individual experience.
39:13 Speaker 00 Yeah.
39:14 Speaker 05 And so with radiation, physicians were not content to just sit around and wait for the scientists to figure it out. They were going to forge ahead with radiation therapy.
39:23 Speaker 00 Regardless.
39:24 Speaker 05 Regardless.
39:24 Speaker 00 They're like, we got this.
39:26 Speaker 05 Yeah. And because radiation was accessible to physicians.
39:31 Speaker 00 Right.
39:32 Speaker 05 And this is reflected in early case reports. So, most experiments with radiation therapy were carried out by physicians in private practice rather than those in academia or public institutions.
39:41 Speaker 00 Okay.
39:42 Speaker 05 Yeah. And because no one could yet explain how it worked, it added to the quote unquote professional mystery of medical practice, reinforcing this boundary between physician and patient.
39:53 Speaker 00 Yeah, yeah, yeah.
39:54 Speaker 05 And to be fair, these physicians weren't drawn to radiation therapy solely because it like lent them this aura of like
40:00 Speaker 00 Right.
40:01 Speaker 05 expertise or anything like that.
40:02 Speaker 00 They wanted to help their patients.
40:03 Speaker 05 They wanted to help their patients. They were sold on the hope that radiation promised.
40:07 Speaker 00 Yeah.
40:08 Speaker 05 Many patients who received radiation therapy truly underwent a transformation. Their pain lessened, their tumors shrank, disfiguring rashes disappeared, and not just when it came to cancer, but like all sorts of ailments where radiation was used. And with radiation therapy, physicians could take action, especially in cases that previously had appeared beyond their help or ability. Gradually, as case reports of radiation therapy accumulated, guidelines were created, like how much radiation to administer, how often, how long, that sort of thing.
40:39 Speaker 00 For what types of different cancers or tumors.
40:41 Speaker 05 Yeah. And hazards were recognized. Radiation, it seemed, could not only shrink tumors, but cause them.
40:50 Speaker 05 Like with radical surgery, initial enthusiasm for radiation therapy gave way to tempered expectations. It's the same thing over and over again. But combining these two therapies improved outcomes, but by the 1930s, those outcomes had largely plateaued. Okay. It was like, we've kind of reached our point. We've come as far as we can with this combination. With these two technologies. Okay. Yeah. Part three, chemotherapy. All right. So, this quote from a 1937 article in Fortune magazine sums up the state of cancer therapy at the time. Okay. Quote, "The startling fact is that no new principle of treatment, whether for cure or prevention, has been introduced.
41:32 Speaker 05 The methods of treatment have become more efficient and more humane. Crude surgery without anesthesia or asepsis has been replaced by modern painless surgery with its exquisite technical refinement. Biting caustics that ate into the flesh of past generations of cancer patients have been obsolesced by radiation with X-ray and radium. But the fact remains that the cancer cure still includes only two principles: the removal and destruction of diseased tissue. No other means have been proved." End quote. 1937. 1937. Okay. "The stagnation in cancer treatments was not due to a lack of will or need.
42:13 Speaker 05 As medicine made headway against infectious diseases, cancer rose to prominence as a leading cause of disability and death in many countries around the world. But the funding landscape for medical research lagged behind the shifting trends in mortality, and cancer had ranked consistently low on the priority list for a number of years." Yeah. "That Fortune article that I just quoted from was not alone in raising the alarm on the limited success for existing cancer therapies and the dismal funding allocated for cancer research. This outcry, which was just like, so many people were like, 'We demand something changed. We demand that you pay attention to this.'" It led to Congress passing a bill to create the National Cancer Institute in 1937. Okay.
42:58 Speaker 05 Yep. And things were, 1937, we're on the eve of World War II, essentially, things slowed down to focus on wartime efforts for, basically until the war ended. Makes sense. Yeah. But, within a few years after the war's end, chemotherapy, the era of modern chemotherapy, began. The first major clue came out of the ashes of World War, not number two, but number one. So while just one among many atrocities committed during the Great War, mustard gas was a nightmare brought to life. Hmm, okay. Yeah, we should do an episode on this sometime. I know, it's been on our list for a really long time. It really has, yeah.
43:37 Speaker 05 Mustard gas is a toxic gas that leaves you asphyxiated, burns. It killed tens of thousands of soldiers and left physical and psychological scars on many more. Physicians studying the long-term effects of mustard gas during World War I found anemia to be a common outcome. It was like the gas had depleted the bone marrow. I know, little, you know, yeah, you know, you know where this is going. Little hint there. Little hint. And this observation may have been lost to history in World War I if an awful tragedy hadn't happened during the Second World War. Okay. In December of 1943, German planes bombed American ships in an Italian harbor.
44:19 Speaker 05 And one of these ships contained like 70 tons of mustard gas. And I don't think mustard gas was really extensively used or used at all during World War II, but I think it was like a, we're gonna bring this just in case. It was like a stockpile just in case. Yeah. When the ship was bombed, of course, all that mustard gas went out into the harbor, went into the, like, the surrounding town, and thousands of people in the area were impacted. Many died. And physicians who were working on the patients who were affected, again, noted this bone marrow depletion and lymph node degradation that was brought on by the gas. So this caught the interest of two researchers who were studying lymphoma.
45:00 Speaker 05 And they were like, what is going on in lymphoma where the lymph nodes in the bone marrow seem to be affected? Is it possible that nitrogen mustards, these compounds in nitrogen gas, could be used to produce the same effect in our patients? Could it, like, attack the malignant white blood cells that are produced by the bone marrow? Right. Sure enough, yeah. Wow. The tumors shrink. Wow.
45:24 Speaker 00 So they were like, we'll use mustard gas to treat our lymphoma patients.
45:29 Speaker 05 Basically.
45:29 Speaker 00 Okay, wow.
45:30 Speaker 05 It wasn't precisely mustard.
45:31 Speaker 00 Right, right, but something similar.
45:33 Speaker 05 Yeah, the same sort of like logic that was like, how do we do this?
45:35 Speaker 00 Yeah.
45:36 Speaker 05 Yeah.
45:36 Speaker 00 Wow.
45:38 Speaker 05 And they had to delay their publication until after the war ended.
45:44 Speaker 00 Yeah.
45:44 Speaker 05 But when the paper finally came out in 1946, it inspired real hope that cancer could be treated with chemicals.
45:52 Speaker 00 Wow.
45:52 Speaker 05 AKA chemotherapy.
45:54 Speaker 00 Chemotherapy.
45:54 Speaker 05 And this was a concept that had been introduced decades earlier, but not really demonstrated clinically.
46:00 Speaker 00 Okay.
46:00 Speaker 05 It was like, we're gonna try ARSEC, we're gonna try all these things, but the tumors never shrink.
46:04 Speaker 00 Super toxic things, but that just weren't specific enough, or weren't whatever enough.
46:09 Speaker 05 Yep, yeah.
46:10 Speaker 00 Interesting.
46:10 Speaker 05 Yeah. Unfortunately, the remissions that were induced by nitrogen gases were short-lived, but it did spur on researchers to investigate other compounds. It was like, finally, kind of like, just getting your foot in the door.
46:24 Speaker 00 Right, like, this concept has merit.
46:26 Speaker 05 Yes.
46:26 Speaker 00 Let's find other things.
46:27 Speaker 05 Let's find other things. And one of the researchers who was excited about this was, has a name you might recognize, Sidney Farber.
46:35 Speaker 00 Farber Institute, Dana Farber Cancer Institute.
46:38 Speaker 05 Yeah. There's the Farber.
46:40 Speaker 00 I was like, where is it in my brain?
46:43 Speaker 05 I knew it was there. Yeah, yeah.
46:45 Speaker 00 Okay.
46:46 Speaker 05 So Farber was trained in pediatric pathology. And, but he found himself intrigued by childhood leukemia, which was a devastating disease that doctors were completely helpless to treat at that time. And leukemia was fairly unique among cancers then, because it could be quantified. You could count your patient's blood cells to see how they were doing.
47:07 Speaker 00 Oh, interesting, okay. Whereas we didn't have markers as much for other cancers.
47:10 Speaker 05 Didn't have as many markers, or it was like, more amorphous, like, what does it mean to have a growth in this tumor, that kind of thing?
47:16 Speaker 00 Right, right, right.
47:17 Speaker 05 And so this made, this made leukemia an appealing target for Farber, because it meant that you could measure how well a certain treatment was working.
47:25 Speaker 00 Okay.
47:25 Speaker 05 If you see your patient's cells go down.
47:27 Speaker 00 Drop.
47:27 Speaker 05 Then maybe that's a good thing.
47:29 Speaker 00 Things are better.
47:29 Speaker 05 Things are better, right. But, and so in the late 1940s, Farber came across some work done by Lucy Wills. Do you remember this name?
47:38 Speaker 00 No, but tell me.
47:39 Speaker 05 You know this name because we've done an episode. Folate.
47:42 Speaker 00 Oh.
47:43 Speaker 05 Our folate episode.
47:44 Speaker 00 Okay, yeah, yeah, yeah.
47:45 Speaker 05 Yes, yes, okay. So she was the physician who discovered that marmite,
47:48 Speaker 00 Uh huh.
47:49 Speaker 05 Specifically, the folate in marmite.
47:51 Speaker 00 Forgot about marmite.
47:52 Speaker 05 I know. Can never forget about marmite. But that marmite could help treat anemia by prompting the body to produce normal blood cells.
48:01 Speaker 00 Right.
48:02 Speaker 05 And so Farber thought that maybe if I administer folate to my leukemia patients, that will prompt their bone marrow to produce normal cells.
48:11 Speaker 00 Red blood cells.
48:11 Speaker 05 Normal red blood cells. But instead, it actually seemed to speed up the leukemia process. It was not good. It was more white blood cells.
48:19 Speaker 00 Okay.
48:19 Speaker 05 Not good. And so he was like, okay, we're going to stop this trial. What's going on here? Maybe it's not that the, like, the bone marrow doesn't seem unable to produce cells. Maybe I just needed to get it to stop making cells completely.
48:33 Speaker 00 Okay.
48:33 Speaker 05 And that's the problem. So instead of giving folate, which would encourage cell production, what if I gave something that was like anti-folate?
48:40 Speaker 00 Anti-folate.
48:41 Speaker 05 That like stopped.
48:41 Speaker 00 Yeah.
48:42 Speaker 05 Cell production.
48:43 Speaker 00 Uh huh.
48:43 Speaker 05 That's what he did.
48:44 Speaker 00 Okay.
48:45 Speaker 05 And what happened were the first chemotherapy-induced leukemia remissions in history.
48:51 Speaker 00 Wow.
48:52 Speaker 05 Which, I mean, I just like, it must have been astonishing to see that.
48:56 Speaker 00 Yeah.
48:57 Speaker 05 We've talked about this kind of thing that happened before, like with the first insulin administered, the first antibiotics administered, just like the sudden switch that destiny is not firm.
49:08 Speaker 00 Right, everything is now changed.
49:09 Speaker 05 Yeah, yeah.
49:10 Speaker 00 Wow.
49:11 Speaker 05 And these remissions, the news of these remissions, had a similar energizing effect on the world of cancer medicine, as did those ones induced by nitrogen musters.
49:20 Speaker 00 Okay.
49:20 Speaker 05 There now seemed to be no doubt that chemotherapy held the key to the cancer treatment puzzle.
49:26 Speaker 00 Okay.
49:27 Speaker 05 And in a sense, it did. The only problem was that cancer kept changing the locks.
49:33 Speaker 00 Yeah.
49:34 Speaker 05 Within a few months, Farber's first patient, three-year-old Robert Sandler, showed signs of recurrence. His leukemia stopped responding to the drug, and he died in 1949. This pattern, a new chemotherapy drug or combination of drugs, shows initial promise, recurrence happens, and then resistance develops, is both familiar and heartbreaking. But it also demonstrates progress, right? Like, how many more months did Robert have with his family that he wouldn't have gotten otherwise? Progress was incremental for early chemotherapy research, but that extra time was precious. And as the 1950s melted into the 1960s, that extra time grew and grew for certain cancers.
50:18 Speaker 05 The first cures were reported during this period, choriocarcinomas, and they were met with initial disbelief. Like, it kind of like, you know, chemotherapies, which showed such initial hope, but then were quickly like, okay, this is clearly a temporary solution, temporary solution. Then to have these, like, full cures were like, wait, it's just gonna come back.
50:38 Speaker 00 Right. I don't want to get my hopes too high.
50:40 Speaker 05 Yes, yeah. But those were largely the exception, right? Overall, results tended to be mixed. There was, you know, you were given more time. That time was not guaranteed, and it was often filled with horrible side effects. And so, there was a lot of, kind of like, this general air, this general aura of disappointment mixed with hope, like, constantly, just like these cycles of disappointment and hope, disappointment and hope for both physicians and the, you know, clinical oncologists working on this, as well as people with cancer.
51:18 Speaker 00 Yeah, and their families.
51:20 Speaker 05 Yeah. And there was a sense, too, that like, the more aggressive the chemo, the better. We need to push our patients' bodies to the act, to the absolute maximum.
51:33 Speaker 00 Because we're fighting a war.
51:34 Speaker 05 We're fighting a war. And this is this, like, this is when the concept of maximum tolerable dose was introduced, where it's like, how much can we administer without killing the patient right now?
51:44 Speaker 00 Oh, God.
51:45 Speaker 05 Was this idea. And then also, like, chemotherapy, the same with radiation, can lead to more cancer-causing effects, or can lead to a higher cancer risk later on, just because you're causing such...
51:57 Speaker 00 Right. You're just damaging cells and killing cells. Yeah, yeah.
52:02 Speaker 05 The cancer treatment world seemed pretty singularly focused on chemotherapy for decades. Much of the billions in cancer funding went towards finding new combos or compounds. And this was driven in part by Farber's partnership with activist and philanthropist Mary Lasker, which led to a huge increase in cancer awareness as well as funding.
52:23 Speaker 00 Okay.
52:24 Speaker 05 Together, they turned cancer into a political and social issue, which was a much-needed transformation. Their approach was guided by the belief that with enough resources, we could brute-force our way into a cure for all cancer. And unfortunately, that cure failed to materialize. Funding for research, no matter how vast, was still a finite resource. And incremental progress in chemotherapy was made at the cost of investment in basic research or development of other treatment modalities. Eventually, as chemotherapy research plateaued, other treatments emerged in the 1980s and the 1990s, informed by our growing understanding of the cellular mechanisms of cancer.
53:06 Speaker 00 Yeah.
53:06 Speaker 05 Which I'm excited to hear you talk about.
53:07 Speaker 00 Yeah.
53:08 Speaker 05 And today, there exists a broad array of cancer therapies that allow oncologists to design a personalized treatment plan for their patients. We still don't have a magic bullet for cancer, for all cancer, and we likely never will. At least, it's hard to imagine that we will, based on the way that cancer works in our bodies.
53:28 Speaker 00 Right, right.
53:29 Speaker 05 But the clinical transformation that cancer has undergone in the past century and a half, it really makes me optimistic for the future. There is, there is no denying that chemotherapy was revolutionary. And it remains a cornerstone of cancer treatment today. But I have to admit that there are parts of its history, at least, that I really struggle with. The belief that you can task-force cancer while disregarding the importance of basic research. And the commercialization, both historically and today, of drug development that discourages looking outside the box, that makes new treatments prohibitively expensive for people. The concept of in-network, I mean, which is, I know this is like a US-
54:12 Speaker 00 It's so American.
54:14 Speaker 05 Thing.
54:14 Speaker 00 It's so disgusting.
54:15 Speaker 05 It is. It is inhumane.
54:18 Speaker 00 Yes, it is.
54:19 Speaker 05 Yep. And there are parts of the story, too, that I feel like are reminiscent of the quote unquote mistaken kindness of the age of radical surgery, where it's like, no, we need to use the most aggressive treatment possible. And in the 1960s and 1970s, when palliative care was kind of introduced as this concept, there was a lot of pushback from clinical oncologists who were like, that's giving up.
54:46 Speaker 00 Yeah.
54:46 Speaker 05 We don't want to give up. We want to fight, we want our patients to fight, we want our, we want us to fight, without actually like maybe considering.
54:53 Speaker 00 Talking with the people and finding out what's happening in your life and what your goals are and what your hopes and dreams are and how this diagnosis and treatment has affected your life.
55:03 Speaker 05 Yeah.
55:03 Speaker 00 Yeah.
55:04 Speaker 05 I mean, I think that there's a lot of, just like we talked about in the beginning part of this episode, there's a lot of push-pull on like what it means to be a physician and a healer and what does that look, you know, healer versus physician, what is, yeah, that's a philosophical question.
55:17 Speaker 00 I know.
55:18 Speaker 05 We're not committed to.
55:18 Speaker 00 Well, I might talk more about it.
55:20 Speaker 05 Okay, great, great, great.
55:21 Speaker 00 Not really, not directly, but.
55:23 Speaker 05 Yeah. There are also parts that sound, you know, too much like a forward march of progress by prescient rebels, right? Like, these people fought against, even though their data showed that they weren't getting anywhere, they continued to, to fight against it. And I'm like, that, I don't know if that's a strength necessarily.
55:41 Speaker 00 Right.
55:41 Speaker 05 Like, they happen to be right about this, but there are many more people in history that were wrong.
55:45 Speaker 00 Right.
55:45 Speaker 05 And they weren't entirely right, anyway.
55:47 Speaker 00 Yeah.
55:48 Speaker 05 And that's just also the way that we tell science stories, I think, that's an issue with that. There's also, I think, a lot, in a lot of these stories, there's a lack of accounting for the human cost and unfulfilled promises that were brought on by all therapies during this time. I mean, we owe so much to early patients, not just of chemotherapy, but of surgery and radiation, and every person who has ever participated in a clinical trial ever, it's incredible.
56:16 Speaker 00 Oh, it's, it is, it is so selfless and it is so beautiful.
56:20 Speaker 05 Yeah.
56:21 Speaker 00 That someone is willing to know, this might not help me, but it will help someone else down the line.
56:26 Speaker 05 Yes.
56:27 Speaker 00 Yeah.
56:28 Speaker 05 And so, yeah, that's, that's one of the parts that I find inspiring.
56:32 Speaker 00 Yeah.
56:32 Speaker 05 And I also find, you know, Farber's passion and vision inspiring.
56:37 Speaker 00 Yeah.
56:38 Speaker 05 There are parts that are uplifting, like those whose lives who have, that have been extended or saved by chemotherapy. And there are parts that are thought provoking, like, where do we go from here?
56:48 Speaker 00 Yeah.
56:49 Speaker 05 Where do we go from here? Cancer treatment, though it has dominated the research scene for decades, is just one way to approach this problem of multicellularity. What if we could minimize our use of aggressive therapy? Or even better, avoid treatments entirely? That's what I'll be talking about next week.
57:10 Speaker 00 Do, da, da, da.
57:10 Speaker 05 How can we incorporate screening and prevention into our picture of cancer?
57:14 Speaker 00 Oh, I'm really excited about that.
57:18 Speaker 05 But for now, I'll turn it over to you, Erin, to tell me how these different types of cancer treatment work.
57:23 Speaker 00 Let me bring us up to speed.
57:25 Speaker 05 Please.
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59:14 Speaker 01 Hello, hello. I'm Malcolm Gladwell, host of Smart Talks with IBM. I spoke with IBM's Ana Paula Acees about what digital sovereignty actually means in the age of AI.
59:25 Speaker 06 AI now moves from somebody operating a system to the technology actually making decisions. So you have to have a much better visibility of what AI is touching, data it is accessing, and where.
59:41 Speaker 01 Hear the full conversation wherever you get your podcasts.
59:56 Speaker 07 Hi, my name is Dr. Longwin and I'm an OB-GYN physician. In November of 2020, I felt a small lump in my right breast. I wasn't too worried about it, but as I was due for a mammogram, I had my colleague order it as a diagnostic. Within three weeks, the mammogram quickly led to a breast biopsy. And two days after my son's sixth birthday, my breast radiologist, friend and colleague, told me I had cancer. It was in the middle of a workday and she was so, so very kind to me. I walked to a private spot behind the hospital and called my husband with the news. Then I pulled myself together and finished seeing patients in the office. I consider myself lucky.
1:00:35 Speaker 06 I caught it early and had a lumpectomy a month after my diagnosis. Four days after surgery, I walked back into my hospital and got my second COVID booster. A month after that, I was back at work and continued to work when I had my week of radiation treatment. I will be five years with no evidence of disease soon, and at that time, I will be able to stop taking Tamoxifen. It's been a journey. Medically-induced menopause is no joke, but I am so grateful to my friends, family, and colleagues who have been nothing but supportive. In my field, I'm the referring physician to the breast surgeon and oncologist. I didn't like being on the other side of it, but I know firsthand now that my patients are extremely well taken care of. Thanks for letting me share my story.
1:01:19 Speaker 06 I know that this may come as a surprise to many of my long-term patients who might hear this, but I'm okay with that. Doctors are human beings too, and cancer doesn't care. Get your mammograms, pap smears, and colonoscopies done. It can save your life.
1:01:35 Speaker 06 Hello. My name is Jasmine, and this is my experience with cancer. To start, I'm going to tell you about my grandfather. My grandfather was a prankster and a jokester, who often got his grandkids in trouble for jokes he started. He was an amateur mixologist, always trying and making something new. He was always outside and loved to meet new people. One of the first signs that something was wrong came from the friends he had made. They noticed that he was rapidly losing weight without seeming to try. This led to a trip to the doctors. On April 16th, 2024, my grandfather was diagnosed with stage IV pancreatic cancer. Shortly after this diagnosis, his children dropped everything and went to Florida to
1:02:18 Speaker 06 be with him and my grandmother. One thing we all wondered about was how this was missed for so long. He had regular visits with the doctor and seemed to be in good health. We quickly realized how sneaky cancer can be. We learned that pancreatic cancer is often misdiagnosed as diabetes, which my grandfather had. We also learned that pancreatic cancer has a very poor prognosis, and my grandfather was only given a couple of months to live. However, in my grandfather's usual fashion, he made a joke. And fought back.
1:02:51 Speaker 06 By the time my grandparents are coming back to their home state of Missouri, his doctor was making plans for the next year, maybe more. We were all ecstatic. Unfortunately, in July, he got a very bad infection that had him in the hospital for days. By the time they managed to clear it, his strength was gone. He was never able to resume his treatments. On November ninth, two thousand and twenty-four, early in the morning, surrounded by family and his loving wife, he passed away. One thing that sucks with cancer is the memories it steals. Seeing my grandfather as a shadow of his former self hurt beyond belief. He was also only a half a year away from my wedding.
1:03:35 Speaker 06 Because of cancer, I never got to show my grandfather my wedding dress. Because of cancer, he never got to meet his third great-grandchild, who was born two weeks later. This whole journey has been a roller coaster. From despair to hope, to saying goodbye one last time.
1:03:54 Speaker 06 I can only hope to see you again one day. Thank you for listening to my story.
1:04:23 Speaker 00 I don't think I'm going to tell you how these work necessarily. In detail. But what I do want to do, I mean, in part because it would be way too much to try and deep dive on.
1:04:35 Speaker 05 Oh, I know.
1:04:35 Speaker 00 Like, all of this.
1:04:37 Speaker 05 Give me the broad strokes.
1:04:38 Speaker 00 I will, thanks. And I want to kind of walk us through some context on like, how we use the tools that you just walked us through.
1:04:47 Speaker 05 Yeah.
1:04:47 Speaker 00 Because those are still the three.
1:04:49 Speaker 05 They are the main treatment modalities, yeah.
1:04:51 Speaker 00 How do we use them today? How is that different than how we use them historically? And then what are some of the biggest new technologies that have now become a mainstay? And a like, integral part of our cancer treatment, but they're new within the last like, ten, fifteen years. And yet now they are like, the standard of care. So, that's what we're gonna do. Okay?
1:05:11 Speaker 05 Okay, great.
1:05:13 Speaker 00 So I talked in the very first episode of the series about how we stage cancers.
1:05:18 Speaker 05 Yes.
1:05:18 Speaker 00 And the staging of cancers is a really important part of this initial process in deciding how that treatment is going to progress and what treatments are going to be recommended, knowing where this cancer came from, what kind of tissue, how far it has spread. All of this has to be taken into consideration to plan your particular cancer treatment.
1:05:38 Speaker 05 Your personalized cancer.
1:05:38 Speaker 00 Yeah. So I'm going to go through the three that you had gone through. I think I have them in a different order, but that's fine. And then we'll move on to like immunotherapies and some of the newer things.
1:05:50 Speaker 05 Okay.
1:05:50 Speaker 00 So surgery.
1:05:52 Speaker 05 Surgery.
1:05:53 Speaker 00 Surgery is very often still a part of cancer treatment. It is totally going to depend on the tumor, if there is a tumor at all, obviously for blood cancers.
1:06:03 Speaker 05 For non, yeah, non solid tissue.
1:06:06 Speaker 00 It's going to depend on where exactly that's located, how far it has spread. But for a very large proportion of cancers, a surgery that removes that entire tumor and aims to remove a margin of healthy tissue. And that's what, when you, when we hear in like your pathology report you get, it says, oh, it had clear margins.
1:06:27 Speaker 05 Clear margins, yeah.
1:06:28 Speaker 00 That means that all of the surrounding tissue did not have cancerous tissue.
1:06:32 Speaker 05 Right.
1:06:32 Speaker 00 So if it didn't have clear margins, it means that tumor is all the way to the edge of the tissue that we got, which means we think we might have left something behind.
1:06:40 Speaker 05 Yeah.
1:06:40 Speaker 00 If, if it's all the way to the margins. If you have clean margins, it means we didn't leave anything behind.
1:06:45 Speaker 05 So what would it say if, if your report did not say clean margins, what would it say?
1:06:49 Speaker 00 It might say that it, like there was cancerous tissue to the periphery.
1:06:52 Speaker 05 Okay.
1:06:52 Speaker 00 Or including the margins or something like that.
1:06:54 Speaker 05 Okay.
1:06:55 Speaker 00 So that would be not good.
1:06:56 Speaker 05 Got it.
1:06:56 Speaker 00 So, um, and so, yeah, that, that is the point. And so that is the goal of any kind of surgery usually, um, is to remove all of the tumor and then some portion of healthy, non cancerous tissue all the way around the tumor. How exactly we're going to do that? What kinds of surgery is going to happen? How much tissue that's going to be? All depends on the cancer. And there's probably a lot that I could have gotten into on the incredible surgical advancements.
1:07:23 Speaker 05 So many.
1:07:25 Speaker 00 There are so many incredible surgical techniques that have been developed in the last few years, decades.
1:07:31 Speaker 05 Yeah.
1:07:31 Speaker 00 Both in terms of understanding how much tissue needs to be removed. Do we need to do radical mastectomies? Very often not.
1:07:38 Speaker 05 Right.
1:07:38 Speaker 00 Like you said, lumpectomies often have similar morbidity and, well, better morbidity.
1:07:43 Speaker 05 Better morbidity.
1:07:44 Speaker 00 Similar survival and recurrence rates. But also, there's been so much advancement in things like minimally invasive surgeries, in the use of robotic surgeries.
1:07:53 Speaker 05 Robotic surgeries.
1:07:54 Speaker 00 Which has allowed for surgery to be a part of cancer treatment where before it couldn't be. If you think of trying to do surgery in a place that's very small and has a lot of really important anatomical structures, like in our head and neck, a lot of times surgery wasn't an option in those areas because they're so small, because there's so much important tissue there. But now with the advancement of minimally invasive and robotic techniques, you might be able to have a surgery, which could significantly improve your outcomes. So there have been incredible, that's all I'm going to say about surgery. It's like, sorry, I'm not doing it justice to all of you surgeons out there, but you do incredible work.
1:08:31 Speaker 05 Oh, my gosh. I mean, it is, it is like, it was reading that quote from 1937 where it's like, "We have the most technologically advanced surgery." And I'm like, "You did then."
1:08:40 Speaker 00 You have no idea what's coming. Well, and like the advancements in plastic surgery and like, you know, reconstructions and things. Like, it's, it's amazing and incredible. So like, shout out to surgeons everywhere. I feel like I probably don't shout them out enough.
1:08:55 Speaker 05 Major props.
1:08:56 Speaker 00 Major, whoop, whoop, to you. And so that, so surgery is a really important part of many, many types of cancer treatment.
1:09:04 Speaker 05 Yes.
1:09:04 Speaker 00 Chemotherapy is the other big time mainstay. And chemotherapy comes in a lot of different varieties these days. But the way that they all work mechanistically is that they kill cancer cells and they do this by being cytotoxic broadly, meaning toxic to cells broadly. The goal with all chemotherapies is that they are targeting mostly rapidly dividing cells. Right. Because we know from our cancer biology and like, basic science research, that cancer cells are continuously dividing. That's one of their big hallmarks.
1:09:43 Speaker 00 And so by targeting these rapidly dividing cells, we are mostly targeting cancer cells. So some of these chemotherapies might work by disrupting DNA replication, right? Some of them might work by disrupting what's called microtubule formation, which is like, how your cells have to arrange the DNA as they divide. Right. So some might target that. Some of them might, there's lots of different, like, specific ways that each chemotherapy drug might interact with those rapidly dividing cells. Right. But across the board, that's what they're targeting. Yeah. Which means that while they target cancer cells, they are also affecting all of our rapidly dividing cells. Like our hair.
1:10:25 Speaker 00 Like our hair follicles, like our GI tract, like our bone marrow, like our skin cells. And so that can cause a really, really wide range of very significant side effects. We can see things like myelosuppression, which is what we saw in those first chemotherapy drugs you were talking about, which means your bone marrow is suppressed. Yep. Which might be a good thing in certain treatments, but also might be a very negative side effect, where you have significant anemia and now you have no immune system to fight off other opportunistic infections and things like that. They all cause things like fatigue and weakness. They're going to have a lot of gastrointestinal side effects, nausea, vomiting, potentially diarrhea, all kinds of things, your hair falling out.
1:11:09 Speaker 00 This is a common side effect of many, many different chemotherapy treatments. There's also a lot that can affect certain cells in our body, like, for example, our heart cells, because they accumulate in some of our tissues. And so you have to be very careful with the dosage that you're given across your entire lifetime. Yep. And so all of this, again, has to be taken into consideration in your specific cancer. Yep. Right? One of the things that I think is probably new and different in how we use chemotherapy today compared to how we maybe used to use it in the past is that there is a very distinct decision on when to use chemotherapy.
1:11:51 Speaker 00 And so we might use different types of chemotherapy with different intentions at different points in someone's cancer journey.
1:11:57 Speaker 05 Yeah.
1:11:58 Speaker 00 So we sometimes might use chemotherapy before surgery. And this is called neoadjuvant, or sometimes perioperative, depending on the exact timing of when you give that. But the goal might be to shrink that tumor before we go in to try and remove it with surgery.
1:12:15 Speaker 05 Right.
1:12:16 Speaker 00 Other times, we might use it after surgery, so adjuvant chemotherapy. And that means like in addition to the surgical removal of most of the cancer tissues, we're going to also do chemotherapy to kind of kill anything that might be left behind, or anything that's more broadly systemic.
1:12:31 Speaker 05 Right.
1:12:32 Speaker 00 Or something like that. And these are not mutually exclusive. You might have one regimen for before and one regimen for after surgery, and you're using these in combination. So that's chemotherapy. Then we still have radiation. And I think it's very interesting to think about how, I mean, it's both old and not old, I guess, radiation is.
1:12:53 Speaker 05 It's old in the history of cancer therapies. But it's not old when it comes to science.
1:12:58 Speaker 00 In the history of medicine. Yeah. But even radiation therapy has come a very, very long way.
1:13:03 Speaker 05 So targeted, yeah. Instead of just like, let's have x-rays available at every shoe store.
1:13:10 Speaker 00 On your whole entire body. Right. Gosh. But especially with advancements, I think, in things like interventional radiology, another shout out to interventional radiologists everywhere, we can deliver radiation now to much more targeted areas. And sometimes this might still be external radiation. And so there's different techniques that, you know, have different names. There's like stereotactic, and sometimes it's called radiosurgery, even though a lot of times there's no surgery involved. There's no cutting open of anything.
1:13:38 Speaker 05 Why is it called that?
1:13:39 Speaker 00 I don't know. Sometimes it's called radiotherapy, sometimes it's called radiosurgery.
1:13:43 Speaker 05 What does surgery mean as a term? What's the root?
1:13:45 Speaker 00 Oh, my God, Aaron, that's a you question.
1:13:47 Speaker 05 No, I know.
1:13:48 Speaker 00 Sorry.
1:13:48 Speaker 05 I don't know.
1:13:49 Speaker 00 But these kinds of techniques in general that use external radiation usually use now very advanced imaging.
1:13:56 Speaker 05 Yes.
1:13:56 Speaker 00 So MRI's or CT scans or something in combination with radiation to deliver that radiation to very specific areas of your body. And that's to minimize the effect on all of your surrounding healthy tissues. And so sometimes what we'll see, and I think people who maybe have been familiar with someone who's had like a head and neck cancer or something like that, or a brain cancer, you might have to have made these very specialized masks.
1:14:23 Speaker 05 Yeah.
1:14:23 Speaker 00 That hold your head in a very, very specific position. And that's made only for you so that that radiation can be delivered to one specific area to target only that tumor.
1:14:36 Speaker 05 Yeah.
1:14:36 Speaker 00 And none of the surrounding tissue.
1:14:38 Speaker 05 Also, you should look up radiolichen therapy because it's very exciting.
1:14:41 Speaker 00 Love it. And so how we deliver that, whether it's external or whether there's something called brachytherapy.
1:14:48 Speaker 05 Hmm.
1:14:49 Speaker 00 Which is where you have radioactive material. So rather than external like beam radiation, you have radioactive material that's either put on something like a wire or a little seed, they call it. And that might be placed inside or very close to a tumor. It might be left there for the long term. It might be there only during the course of a procedure. Again, this is where things like interventional radiology can really play a huge role in targeting tumors that are even deep inside the body. Which is incredible. And we have other techniques now besides just radiation that I think kind of fall into this kind of procedural category where we might use heat or electricity or even ice.
1:15:31 Speaker 05 We talked about this.
1:15:33 Speaker 00 In one of our, uh, the
1:15:35 Speaker 05 Hypothermia episodes.
1:15:37 Speaker 00 Yeah, so we can do that.
1:15:39 Speaker 05 Okay.
1:15:39 Speaker 00 Cryotherapy.
1:15:40 Speaker 05 Yeah.
1:15:40 Speaker 00 Directly to tumors. They use this for things like liver, some liver cancers or liver tumors and things like that.
1:15:45 Speaker 05 Whoa. Why, mm, okay.
1:15:48 Speaker 00 It's easy to access. That's one of the reasons.
1:15:50 Speaker 05 Okay.
1:15:50 Speaker 00 Yeah, and livers have really good blood supply. So then like the surrounding tissue is still gonna have good blood supply, I think is part of it. Um, it's also just a very common place that you get tumors. So it's like that. So we've come a really long way in our use of radiation and radiation still has very significant side effects, especially we use it a lot in, you know, either anal or rectal cancers and like the after effects of radiation on the surrounding tissue can be very severe, um, in the long term. So it's still not by any means a perfect system.
1:16:27 Speaker 05 No, I think, I, I think this is something that like chemotherapy in general comes up as a what, what will we look back on in the future and go, whoa.
1:16:37 Speaker 00 Whoa, this is what we did?
1:16:39 Speaker 05 This is what we did. I mean, and again, like this is the like people are, it's not like people are working on this as a torture device.
1:16:46 Speaker 00 No.
1:16:47 Speaker 05 People, physicians worked on this because they wanted to help their patients.
1:16:50 Speaker 00 To save people's lives.
1:16:51 Speaker 05 Patients participated in this because they wanted to have their own lives extended or the lives of other future cancer patients. Like it's, yeah.
1:16:59 Speaker 00 Yeah, it's, it is, but I, I agree.
1:17:01 Speaker 05 I know, I know. It's really, it's complicated.
1:17:03 Speaker 00 It really is. So those are the kind of big three that we still use today. But there's a lot more ways now that we have to help treat and prevent recurrence of cancers going forward. So.
1:17:18 Speaker 05 Yeah.
1:17:19 Speaker 00 I mentioned.
1:17:19 Speaker 05 Immunotherapy?
1:17:20 Speaker 00 Did it? Yeah, well, let's get there.
1:17:21 Speaker 05 Okay, okay, we're doing more, sorry, sorry.
1:17:23 Speaker 00 One short thing before we go immunotherapy.
1:17:25 Speaker 05 Okay.
1:17:25 Speaker 00 Here we go. Ready? Um, the only thing I wanted to mention aside from immunotherapy before I dig deep into that is that for some cancers, we test for, and I mentioned this in, I think, the last episode, for some cancers, we might test for things like hormone receptors.
1:17:39 Speaker 05 Yes.
1:17:40 Speaker 00 So we know for Some prostate cancers, for some breast cancers, these might be very hormone sensitive. And so for some people, part of their treatment might include hormone blockers. And this might be to halt the growth and also to prevent recurrence of cancers. You know, kind of maybe towards the end of a therapy, or in some cases, like throughout the entire course of their cancer treatment. And so that's a very relatively, I mean, hormones have been around forever.
1:18:05 Speaker 05 Yeah, I mean, the kind of the conceptual design of hormone therapy has been around since probably like the 1930s, something like that. When hormones were like becoming a big thing.
1:18:14 Speaker 00 The thing.
1:18:15 Speaker 05 The height of endocrinology, or at least like the beginning excitement around it. But I don't think, like, I'm actually not sure when it became more of a routine or standard of care for certain cancers.
1:18:26 Speaker 00 Probably depends on when they figured out that these cancers were sensitive to hormones for their growth. But you are right, that I think that one of the biggest ways that we've changed in how we target cancers today is the advent of immunotherapy. So I want to talk a little bit about what that means, because it's a very broad category. And depending, I think, on who you talk to, they might be more generous in what counts as immunotherapy. And I'm going to be very generous in what we count as immunotherapy. And that means anything that is targeting the immune system with a goal of using the immune system to help target our cancers.
1:19:02 Speaker 05 Right, like, hey, he's over there.
1:19:04 Speaker 00 Right. And so that might be in a relatively passive way. Passive doesn't quite work, but that's correct, actually. And that might be something like monoclonal antibodies. So monoclonal antibodies are things that we use very commonly now for a lot of different types of cancers. And these are antibodies that we give to a person that target specific cell receptors on their particular cancer in order to help our immune system recognize them. The reason I say passive is because it's like the antibodies are doing the flagging.
1:19:38 Speaker 05 Yeah, you're not telling, the immune system is not like, you're not going, come on, come on, come on, do this. It's like, we've got some more.
1:19:43 Speaker 00 Putting these flags on themselves. But so that's an amazing way that we have found for a lot of different types of cancers. We have monoclonal antibodies for breast cancers, for hematologic cancers, for a lot of different, for blood cancers, for a lot of different types of cancers. But even you could think of a bone marrow transplant
1:20:05 Speaker 05 Yes.
1:20:05 Speaker 00 as a type of immunotherapy. A bone marrow transplant is wiping out the cancerous bone marrow and replacing it with a new bone marrow. That is immunotherapy. All of this is leveraging our body's own immune system because cancers are incredibly good at evading this. They can manipulate a lot of our typical defenses. So the aim of a lot of the newest forms of immunotherapy is to reactivate a lot of the immune responses that are turned off or altered in some way or another during cancer. For some cancers, we can identify very specific receptors.
1:20:49 Speaker 00 For example, like HER2 new, which a lot of people may have heard of in breast cancer. It's not only in breast cancer. It's also in gastric cancers and things. But that's a specific receptor that is present on some cancers that we have an antibody that can target. And that can boost our immune system's response to targeting that cancer.
1:21:06 Speaker 05 Yeah.
1:21:07 Speaker 00 So by identifying those kinds of receptors that we might be able to target, we can help our own immune system recognize those cells as being damaged or as being cancerous and eliminating those cells. So monoclonal antibodies are one. There's another type of immunotherapy that is very, very common now that's really quite new, like in the last, I think, probably 10 or 15 years. And these are called checkpoint inhibitors.
1:21:35 Speaker 05 Yes, yes.
1:21:37 Speaker 00 And these basically help to, again, turn back on a mechanism that cancer cells usually turn off. So cancer cells turn off this ability for our normal T cells to recognize cancer as cancer. So checkpoint inhibitors turn that back on and make our T cells go, oh, wait a second.
1:21:58 Speaker 05 Wait.
1:21:58 Speaker 00 I see this and you're not right.
1:22:00 Speaker 05 Yeah. How could I have missed this?
1:22:02 Speaker 00 Exactly, exactly. And so those are very incredible. And we have a number of different checkpoint inhibitors that target different checkpoints, as it were, because different ones might be turned on and off in different types of cancers. Another very, very exciting, super new kind of area of immunotherapy that has shown a special promise and has the most like approved treatments for blood cancers like leukemias and lymphomas and myelomas is something called CAR T cell therapy.
1:22:31 Speaker 05 I know CAR T cell therapy.
1:22:34 Speaker 00 This is very exciting and too detailed for me to like go dig deep on, but it basically involves engineering your own T cells. So taking out immune cells from your body, white blood cells from your own body, adding things to them, putting them back in your body with these specific types of receptors on them that target your specific cancer.
1:22:58 Speaker 05 Basically saying, let's engineer these cells to become, you know, cancer detectors.
1:23:03 Speaker 00 Cancer detectors.
1:23:04 Speaker 05 Yeah.
1:23:05 Speaker 00 In a way that they aren't right now.
1:23:06 Speaker 05 Yes.
1:23:06 Speaker 00 And what's really fascinating is that they've been able to do this, and again, I've got some papers if you want to dig really deep on the mechanisms here because it is really fascinating, but they're able to do this in a way that also helps sort of jump over several hoops that our immune system usually has to jump through.
1:23:23 Speaker 05 Right.
1:23:23 Speaker 00 So that you don't have to like convince everyone in your immune system to get on board.
1:23:28 Speaker 05 Cut through that red tape.
1:23:29 Speaker 00 Exactly.
1:23:29 Speaker 05 And just get right to the cancer.
1:23:31 Speaker 00 Just get right to the cancer. So that's very incredible and there's a lot of interest in being able to use this type of therapy for solid tumors as well. So far, as far as I know, we don't have any therapies that are CAR T cell for those yet.
1:23:43 Speaker 05 Okay.
1:23:44 Speaker 00 But I do think that that's one of the big ones on the horizon and I could be wrong about that. I might've just missed some super new research, but it's very like immunotherapy in general broadly and all of these specific types of immunotherapy, and I'm sure I'm missing some, really are incredible in that they recognize this knowledge of basic cell biology and the basic cancer biology of how they are evading our immune system and are looking for ways to use our own immune system. Get it back online, the way that it ought to be.
1:24:15 Speaker 05 Right.
1:24:16 Speaker 00 So I think that that's really incredible and they show so much promise.
1:24:19 Speaker 05 Well, and I think it's just like thinking about the millennia of evolution, thinking about like last week's episode and how cancer cells have to overcome, have to have to evolve so many different mutations, so many different ways to then evade the immune system, proliferate, all these different things.
1:24:37 Speaker 00 Yeah.
1:24:38 Speaker 05 Our immune system does an incredible job of usually preventing that from happening in the first place.
1:24:43 Speaker 00 Exactly.
1:24:44 Speaker 05 And so if we can just like be like, you know what, we have a really great cancer detector and cancer eliminator here, let's just give it a little bit of a boost.
1:24:53 Speaker 00 Right, let's leverage what we've already got in a way.
1:24:55 Speaker 05 Yeah.
1:24:56 Speaker 00 And sometimes, very often, these immunotherapies might be used in combination with chemotherapy.
1:25:02 Speaker 05 Right.
1:25:02 Speaker 00 And they might actually help to improve chemotherapy outcomes or mitigate some of the resistance that we see to chemotherapy. So as one example, if a chemotherapy drug is inducing DNA damage, and that's the main thing that it's doing, is damaging the DNA, but the tumor cells that are there have these mechanisms that resist our immune system's ability to detect damaged DNA.
1:25:27 Speaker 05 Okay.
1:25:27 Speaker 00 Where the tumor itself is like, it doesn't matter how much you damage me, I'm still going to proliferate.
1:25:32 Speaker 05 Right, right, right.
1:25:33 Speaker 00 Then immunotherapy might be able to help make those damaged cells more visible to the immune system.
1:25:38 Speaker 05 Yeah, yeah.
1:25:39 Speaker 00 So they kind of can work in tandem and in conjunction like that.
1:25:42 Speaker 05 Right.
1:25:42 Speaker 00 Which I think is pretty incredible. There are a number of papers from less than 20 years ago, 10, 15 years ago, 2011 and 2016, I found a few, that are all about immunotherapy that say, this is the beginning of the end of cancer. We've done it, we've done it. And it's not that...
1:26:03 Speaker 05 Haven't we learned this lesson?
1:26:05 Speaker 00 I know. It's not that the hype isn't warranted, because again.
1:26:09 Speaker 05 Sure.
1:26:10 Speaker 00 Immunotherapies have shown, have made incredible bounds, they have made it so that some cancers that used to have absolutely no treatment can now be put completely into remission, if not cured, in some cases, because of immunotherapies. So it's not that the hype isn't warranted, but for every promising aspect of these therapies, there are also side effects. There are also unforeseen consequences. And very often, the reality that we see is that the successes in early or preclinical trials don't always replicate on a big scale. And cancers still evolve and adapt even to our best immunotherapy efforts. Not everybody is going to respond to them.
1:26:53 Speaker 00 Not everyone is going to respond in exactly the same way. And so it really is that. And all of the papers now about like, what is the future of oncology and the future of, you know, cancer treatment? It is this idea that you had said, Erin, of personalized or precision medicine.
1:27:10 Speaker 05 Precision medicine.
1:27:12 Speaker 00 And for cancer therapy, what that means is that no two cancer treatments might be exactly the same. We have to find a combination of medicines, of immunotherapy, of chemotherapy, hormone therapy, surgery and radiation, and whatever we come up with in the future to treat your specific cancer and adapt that treatment to your cancer as it goes.
1:27:36 Speaker 05 Yeah.
1:27:37 Speaker 00 And you mentioned, Erin, this idea of adaptive therapy. And there's a lot of really strong preclinical evidence for this idea of adaptive therapy, basically not aiming for cure.
1:27:49 Speaker 05 Right.
1:27:49 Speaker 00 But just sort of keeping things as they are. And it's not something that's used widely. It's mostly all in clinical or preclinical research at this point. But I think that this concept is so fascinating, but requires a complete paradigm shift in how we think about cancer.
1:28:10 Speaker 05 Yes.
1:28:11 Speaker 00 How we are measuring success in cancer treatments and how we like conceptualize cancer, period.
1:28:19 Speaker 05 A hundred percent.
1:28:20 Speaker 00 Right?
1:28:20 Speaker 05 Absolutely.
1:28:21 Speaker 00 And I think that this is a really important framework because like we've said so many times by this point, like some cancers we can cure. Most cancers we cannot.
1:28:33 Speaker 00 But often, when we go into an oncologist's office, that is still the hope.
1:28:39 Speaker 05 Right.
1:28:39 Speaker 00 And it is not necessarily clear that a therapy, the goal might not even be curative treatment, but whether that goal is communicated clearly to the people undergoing it and their families, may or may not actually happen. And, you know, we do have palliative care and palliative therapies that are often used. And I have so much love for palliative care and palliative care physicians. But I think that they are seen as a last resort for many. They are seen as giving up. There's often kind of clashes, unfortunately, between oncologists and palliative care physicians in what their goals are.
1:29:22 Speaker 05 Right.
1:29:22 Speaker 00 Whether the goal is, you know, reducing the cancer or whether the goal is the patient's goals.
1:29:28 Speaker 05 Right.
1:29:29 Speaker 00 And their family's goals and what you want out of your life and things like that. And so I think that these ideas of, of using therapies with different goals in mind, it has to come a really long way before we're kind of there.
1:29:43 Speaker 05 It does. And I think that like part of the, the challenge with it is the way that cancer treatments, and again, I'll throw Nixon under the bus. I don't really care.
1:29:53 Speaker 00 Yeah.
1:29:54 Speaker 05 But this idea of like war on cancer, we throw enough money at this problem, we will come up with a solution. And then that fail to deliver on that.
1:30:01 Speaker 00 Yeah.
1:30:02 Speaker 05 Promise, on that all of these money spent, that money was not ill spent at all.
1:30:06 Speaker 00 No.
1:30:06 Speaker 05 The problem was the messaging in the first place.
1:30:09 Speaker 00 Exactly.
1:30:09 Speaker 05 And saying, there is going to be this thing. And so then when that thing doesn't materialize, there's disappointment. And there's a lot, loss of faith really sometimes in the scientific and medical community because what was promised has not been delivered without seeing what actually has been delivered.
1:30:26 Speaker 00 Right.
1:30:26 Speaker 05 Which is incredible. And so this reframing of cancer as this unavoidable consequence of multicellularity or this consequence of multicellularity, maybe not entirely unavoidable, but. This thing that maybe is cure the goal. What is the right goal? How do we measure success? All of these different things are not, have not really had a seat at the table when it comes to the war on cancer.
1:30:50 Speaker 00 Exactly.
1:30:50 Speaker 05 Quote unquote.
1:30:51 Speaker 00 Exactly.
1:30:51 Speaker 05 And so I think that has been, that has contributed so much as well to the fear surrounding it.
1:30:57 Speaker 00 Yeah.
1:30:57 Speaker 05 Yeah.
1:30:58 Speaker 00 I think one of our listeners actually wrote in, and I really love the way that he framed this idea. Because he was saying that all of these analogies saying that we have to fight cancer, that it's this battle. This imagery implies that if you've lost, it's because you didn't fight hard enough.
1:31:13 Speaker 05 There are winners and losers.
1:31:15 Speaker 00 Exactly.
1:31:15 Speaker 05 And you didn't fight.
1:31:16 Speaker 00 Exactly. And so I'm going to quote him. Thank you so much for sending this email. He said, quote, "Cancer is not something that you fight. It's something you endure." And I think that that's just so powerful because it's true for so, so many people, you know? Despite how much progress we have made, and I don't want to understate how much progress we have made.
1:31:36 Speaker 05 Right.
1:31:36 Speaker 00 There are also still huge disparities in cancer treatment on so many different levels.
1:31:44 Speaker 05 So, so many levels.
1:31:46 Speaker 00 On one level, not all cancers get the same amount of research funding.
1:31:51 Speaker 05 Right.
1:31:51 Speaker 00 So not all cancers are as well understood. So we have these new paradigm shifting treatments like CAR T cell therapy for some cancers. And others, we have nothing new under the sun. And for cancers where new or exciting or very promising treatments still exist, these are not universally available by any means. So where you live in the world, where you live in this country, in the United States, whether you live in a big city like Boston, where you have your pick of cancer treatment centers, or if you live in a state that has no access to, you know, clinical oncology or an academic medical center.
1:32:34 Speaker 00 In this country, what insurance provider you have.
1:32:37 Speaker 05 Yeah.
1:32:38 Speaker 00 And whether or not they are willing to cover any of your treatments or what is recommended.
1:32:43 Speaker 05 Right.
1:32:43 Speaker 00 Your race, your education level, your socioeconomic status. All of these things affect your access to treatment and have affected the outcomes that we see in cancer treatments.
1:32:57 Speaker 05 Absolutely.
1:32:57 Speaker 00 And cancer mortality. And this has led to really huge disparities in especially cancer mortality, but as well as like diagnosis.
1:33:06 Speaker 05 Which contributes to mortality.
1:33:07 Speaker 00 Exactly, exactly. We'll talk more about that next week. But what we see in the US is that black Americans and Americans who live in rural areas and Americans with lower education levels or lower socioeconomic status, which often go hand in hand, have significantly higher mortality rates across almost all cancers. And we'll talk in a lot more detail about that later. So I think it's true what you said already, Erin, and what actually Lindsay Fitzharris said in our book club episode, that like, are we going to look back on cancer treatments, how we do it today in 30 or 50 years and say, whoa, I can't believe that we did these things.
1:33:48 Speaker 00 And at the same time, the way that we treat cancer today is drastically different than how we treated it 10, even 20, even five years ago for some cancers.
1:33:59 Speaker 05 Yeah.
1:33:59 Speaker 00 So it's really, it's really, really incredible how much progress has been made. And this has been made because of funding for basic research. This has been made because of funding for clinical trials. And right now, that funding has been cut in the US.
1:34:18 Speaker 05 Hugely.
1:34:19 Speaker 00 Hugely. Nearly $4 billion so far in cuts to the National Institutes of Health and NSF, including over $790 million from the National Cancer Institute alone. And what is so scary is that the therapies that we have today came from research that was done 5, 10, 15, 20 years ago.
1:34:40 Speaker 05 There's a time lag to all of this.
1:34:43 Speaker 00 So we will not know the impacts of all of the cuts that we have seen to basic research and clinical research.
1:34:51 Speaker 05 Yeah.
1:34:52 Speaker 00 That has happened this year and last year for the next five or 10 years. But there will be impacts.
1:34:58 Speaker 05 It's. It's investment. Like, there is no other way to look at this. This funding for basic research, funding for clinical trials, funding for any kind of scientific medical research is investment in our future.
1:35:13 Speaker 00 Exactly.
1:35:13 Speaker 05 And the fact that that's being cut, I mean, yeah. What more can we say that hasn't been said? It's shortsighted. It is ridiculous.
1:35:20 Speaker 00 It is.
1:35:21 Speaker 05 It shows a complete lack of understanding of the way that the world works and how each individual person has benefited directly from basic research.
1:35:30 Speaker 00 Yes. So, a huge thank you to everyone who has ever participated in clinical trials, in any kind of research trials, all of you who are working on research, who are doing that research. Like, it cannot be overstated how impactful that is and will be.
1:35:48 Speaker 05 Yeah.
1:35:49 Speaker 00 And, thank you. That's all I have to say.
1:35:51 Speaker 05 Yeah, I had a little note here, too, that was like, thinking about the history of treatment and how far we've come, and how many people have been involved
1:35:59 Speaker 00 Exactly.
1:36:00 Speaker 05 in that, in the fundraising for it, in the raising awareness of it, in the participating in clinical trials, in the being willing to organize a clinical trial.
1:36:07 Speaker 00 Yeah.
1:36:07 Speaker 05 Everyone who has been support staff, the PIs, everything.
1:36:11 Speaker 00 It takes so many people.
1:36:13 Speaker 05 Yes.
1:36:13 Speaker 00 And it is so valuable, and hopefully this will change, and it will continue to be valued, as it is in other countries and things like that. But I have a lot of interesting articles, if people want to read more, about what we anticipate some of those impacts might be.
1:36:29 Speaker 05 Yes.
1:36:29 Speaker 00 So, that's cancer treatment today, Erin.
1:36:33 Speaker 05 Cancer treatment, a survey of the existing treatments.
1:36:36 Speaker 00 Yeah.
1:36:38 Speaker 05 That was great.
1:36:39 Speaker 00 Thanks.
1:36:39 Speaker 05 Yeah. Sources?
1:36:41 Speaker 00 Yeah, yeah. I mean, people want to read more. I got a lot, a lot.
1:36:46 Speaker 05 Uh, yes. Um, let's see. Again, I'll shout out The Emperor of All Maladies, great story about the, by Siddhartha Mukherjee, great story about the history of different cancer therapies, but especially chemotherapy is the main focus there. To learn more about the history of surgery, Wild and Posten, well, okay, Wild et al. from 2015 called the, titled "The Evolution of Cancer Surgery and Future Perspective," by Hader from 1998, "The Clinic as Laboratory: The Case of Radiation Therapy, 1896 to 1920." Really interesting about this transitional shift between Evidence-supported research and how that kind of flew in the face of
1:37:30 Speaker 00 How we used to do.
1:37:31 Speaker 05 Experience-supported decisions.
1:37:32 Speaker 00 Yeah.
1:37:33 Speaker 05 Then by Gal Marini et al. from 2012, "Cancer Chemotherapy: A Critical Analysis of Its 60 Years of History."
1:37:40 Speaker 00 Okay. I have quite a lot of papers for this one, including a lot of specifics on different types of cancer. So if you're interested in like breast cancer treatments today, colon cancer treatments today, I have a lot of papers that you could look at those details. But some broader ones, I mentioned, there was one from 2011 by Melman et al. in Nature called "Cancer Immunotherapy Comes of Age," which was a really interesting read. I have one on CAR T-cell therapy from Patel et al. 2025. That's called "From Concept to Cure: The Evolution of CAR T-cell Therapy." That goes into a lot more detail on what exactly that is. I have a couple of other papers on adaptive therapy and things. But I also just want to give a shout out to two, these are not peer-reviewed. These are articles that were written by Nature staff members.
1:38:24 Speaker 00 But they're about kind of trying to forecast what some of the impacts of these funding cuts might be.
1:38:30 Speaker 05 Yeah.
1:38:31 Speaker 00 Because we can't know right now. And so these are kind of interesting papers that you could take a look at. They're just sort of articles, they're not, again, not peer-reviewed, but they're interesting. And again, I got a long list here. So go to our website, thispodcastwillkillyou.com to see all of the sources from this episode and every single one of them.
1:38:48 Speaker 05 So we've read so many papers.
1:38:54 Speaker 05 Thank you again so much to the providers of our firsthand accounts.
1:38:57 Speaker 00 Yeah.
1:38:57 Speaker 05 It means the world.
1:38:58 Speaker 00 It really does. Thank you. Also, thank you to John and Brett, our respective husbands.
1:39:03 Speaker 05 Yes.
1:39:04 Speaker 00 For all of your help in letting us talk your ear off about this. I also want to shout out my friend Julia, who is a palliative care physician. And she let me talk in her ear for a long time about my feelings about all of this. So thank you, Julia.
1:39:17 Speaker 05 Thank you, Julia. Thank you to Bloodmobile, who provides the music for each episode, this episode and all of our episodes. Wow, I haven't said that in a while in that way.
1:39:25 Speaker 00 You know, since a week from, since a week today. Thank you to everyone at the Exactly Right Studios where we're recording this today. And thank you to Tom and Leanna and Pete and Everyone who's here today, Jessica and Sabrina and Boomer.
1:39:39 Speaker 05 Corey, yes, everyone.
1:39:40 Speaker 00 Corey, everyone.
1:39:41 Speaker 05 Yes, thank you, thank you. And thank you to you listeners. You make us make you make this happen. You thank you for listening.
1:39:49 Speaker 00 Yes.
1:39:49 Speaker 05 Participating in this podcast in some way.
1:39:52 Speaker 00 We really appreciate it.
1:39:52 Speaker 05 How do we not do this better at this point, Erin?
1:39:55 Speaker 00 Listen, we're trying.
1:39:56 Speaker 05 We're trying. Thank you patrons also. Your support means everything.
1:40:00 Speaker 00 It does.
1:40:00 Speaker 05 Thank you, thank you.
1:40:01 Speaker 00 Thank you.
1:40:01 Speaker 05 Until next time, wash your hands.
1:40:04 Speaker 00 You filthy animals.
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