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.
Do you know that you can live without a jugular vein? Those were the first words my surgeon told us after he removed sed vein during my second excigen surgery for sway MISSL carcinoma six months earlier. The newly discovered cancer was isolated to my tongue and lymph. Notes the cancer was brought on by the human papaloma virus HPV. As a gen xer, I probably got it long ago. However, my children are likely to be spared HPV and this
kind of cancer because of the gardess of vaccine. The cancer was removed with good margins me and that I've probably gotten at all. Then came the radiation to sweep up any stray cells hanging around. I received the largest dost possible, thirty sessions directed in my neck and mouth. Before radiation began, I was told there was a deterioration risk to surrounding bone structures. I brushed it off, thinking save my life. Nothing else matters. However, the radiation did
not stop an immediate recurrence. That's when it was drapped around my jug of the rain. Then I began chemotherapy. This required me to mask after each treatment so as not to contaminate the air with chemo. I was only a few treatments in when the world shut down due to the cod pandemic. Because the public was buying up medical protection, supplies on cology ran short and I had to source my own masks. Chemo worked where radiation had not. I'm in a remission, but cancer is still a part
of my life. As predicted, the large radiation dose ravage the bones of my jaw. It's been seven years since cancer, and I still faced an extensive eight hour surgery just to refer the damage from treatment itself. The inevitability is that without this procedure, it's only a matter of time before my jaw simply breaks. There was no saving my teeth. Eating without them and with a partial scarred tongue is difficult and limited. I needed physical therapy to learn to
swallow again. Since Stentser's a contraindicated I'll be living with the stigma and drawbacks associated with toothlessness. For the rest of my life. Still beats being dead.
My name's Louise Baines and I have stage four triple negative breast cancer. I was first diagnosed stage three eight years ago at the age of thirty nine. I have the standard treatment chemotherapy, surgery, radiotherapy was eventually back to some semblance of then in twenty twenty three, I found a suspicious lump in my armpit, a new lymph no tumor. I had more surgery, more chemo, but at the end of that year, sadly, a ct scam found widespread bone mets and lymph no tumors in my chest. My world
fell apart for the third and most ominous time. I was told I'd need to be on treatment for whatever time I had left, thought to be around two years, treatable to a point, but not curable. Seeing palliative chemo on my notes was a bit of a shock. Triple negative is aggressive and can become resistant to treatment. My first line of therapy, chemotherapy and immune therapy got me stable, pretty much obliterated all my bone mets, but I had progression after a year, so I moved on to a
new drug. This was a targeted chemotherapy that I had only been around for a few years. It gave me hope to find some of the ladies on that original trial were still stable or no evidence of active disease even after five years. I took part in a clinical trial with my primary chemo which added an extra trial drug into the standard treatment, and I became fascinated with the science behind the treatment. Researching the history and development
of each drug became really interesting to me. That first study didn't show any better outcomes than standard treatment, sadly, but being part of the research made me feel like I was helping in some small way. After my second line of treatment started to show resistance after another year, I decided to look for another clinical trial. I only have a few options left for suitable chemos, and while I'm still pretty fit and well, I don't want to
use them all up too fast. I was approved for a trial at the Royal Marsden in the UK, and I'm being really well looked after. I'm on my second cycle of a targeted immune therapy plus a standard immune therapy similar to what I had as my first line. It's a phase one expansion trial, so the drug has shown someone promising results in one type of cancer and is being expanded to include other difficult to treat cancers
like mine. I'm quietly hopeful. I'm now two years into my diagnosis, and I didn't expect to still be here. Research is very important to me, and I will be forever grateful for the extra time I've been given with my son, my husband, and my friends. Statistics haven't quite caught up with the current treatment, so I wouldn't recommend googling for a prognosis. According to that, I should be
in the ground long ago. But right now I'm living well and hopefully we'll continue to do so for as long as I can thanks to science.
Thank you so so much for sharing your story with us, and a huge thank you to everyone who has written in with their experiences. It is, I mean, it is so incredibly meaningful that so many of you are willing to put yourselves out there and share such an intimate part of your lives. These first hand accounts are truly, truly are the backbone of this podcast.
They really are, Like this podcast would not be the same without all of you and all of your stories. And we have a lot more that we're going to be sharing throughout this episode and throughout this series that we're putting together. So truly, thank you so much to everybody who took the time to submit your story, to write in to record yourselves. We really wish that we could have included every single story because they all mean so much to us, So thank you.
Yeah. Hi, I'm Aaron Welsh.
And I'm Erin Alman Updike and.
This is this podcast will kill you.
Welcome to our series on cancer.
On cancer. Yeah, well I don't know this, I mean such a big topic. I mean, we may the decision because it is. It is a checked so many people. It is such a big topic and if we ever want to go into certain cancer episodes in the future, we need to lay a foundation.
And that's what we're doing. That's to today.
Right right, We have got four absolutely info packed episodes ahead of us where we're going to be covering this tremendously huge, monumental.
Topic and only four episodes.
In only four episodes, Oh, there's like a lot of material here.
Oh yeah, we'll yeah, you can't see our folders, but this is.
One episode's worth. Yeah. But when we first decided that we wanted to do these episodes, we immediately kind of okay, we asked ourselves what do we want to cover, how do we want to approach this, what aspects to focus on, and how to organize them in a way that made sense so that we could just like again, lay a foundation. So our goal with this series is to do that, is to kind of give you the background information about what cancer is, how we treat it, and also where
do we go from here? And so with that in mind are our first episode The one today explores what cancer is, both conceptually and clinically, and how we came by that knowledge. The second delves into what's happening inside and outside of our bodies to make cancer so prevalent, and the third is all about treatment, which.
Is a lot big it's a big top.
And the fourth and final episode surveys the current landscape of cancer around the world and asks what can we do about this?
Where do we go from here? So it's a lot there's a lot of ground that we're going to be covering, but as much as we are covering, there is a lot that will necessarily remain unexplored in this first of our cancer series. So please everyone listening and watching, No. Two things Number One, we have a really huge list of sources for these episodes that we put together, so if you want to read more, there is tons that you can look up and read just as a starting point.
And number two, these are not the only cancer episodes that we've ever done that we ever will do. We have a lot of plans to cover a lot of the individual cancers that we'll be talking about and touching on in this episode. So we also would love to hear from you if you have particular cancers or particular topics that you want to hear a lot more about. I know, just like we know that we'll need to do callon Cancer very soon.
Yeah, and we will be doing it. Let's tell your thoughts. Like again, we always ask for thoughts, but like especially in this what do you want to hear more about exactly exactly and as you'll hear you know, know to cancers or experiences with cancer are alike. And so we are again so grateful to our first hand account providers for showing us just a sample really like a sample of the diversity of ways that cancer can touch our lives.
You know, in these episodes, what we focus on is primarily cancer as like a biological phenomenon, not necessarily the experience of cancer. And so we are again eternally grateful to all of you who have provided this important context and sharing your experience from of someone who has been diagnosed with cancer, who's undergoing cancer treatment, who's has a loved one who has cancer, who is a caregiver, you know, all all of these different facets that are so integral to the experience.
We really like can't say enough I know how much these first hand accounts mean absolutely everything to us, and in this cancer series especially, it's been so meaningful to get to hear from so many of you, So thank you again.
Okay, one more piece of business, just a little bit, and that is quarantine time. Quarantiny time, actually though it's play and that's.
Plassy Berita time. I guess this is an announcement.
That we're making kind of is we've.
Been doing this quarantiny business since we started the podcast, and it's actually one of the things that really clinched the idea of doing this podcast. Would kill you, because Aaron came up with the name Quarantini and it was
too good to pass up. But we thought that as we'll learn, so we've talked about alcohol before and the problems with alcohol in the past, and so we thought that this series today, starting today, would be a fitting time to no longer include alcohol in our quarantini recipes. So they're technically all going to be plassy burritas.
They are they are. I mean, we're still going to use the term quarantini because it's really good. I can't let it go. I can't let it go.
But I'm also quite proud of plassy burrita. That's really good.
And I remember when that we came up with that. Yeah, it was on the It was on the fly.
Yeah again, it was I think while we were recording, wasn't it. Yes, Yeah, that was good.
Yeah, yeah, Okay, So what is our quarantining? What is it for the series?
Aron?
We're drinking the crab, the crab because cancer. Yeah, that's what it is. Yeah, it's basically an aphagado. Yes, I actually really wish that we had one. That would be so much.
I could use a little caffeine at a little boost.
Yeah, yeah, but you can. You know, we'll still post on our Instagram or whatever.
Wow, we'll bringing endorsement of our social media listen, still post.
Our social media game could probably use some work at this point, but I know.
We will post it there and you know it's fine. You can look it up the recipe, but also look up the crab because you know we did make the effort.
You mean our version of ye yeah, yeah, yeah, exactly. Yeah. So follow us on social media if you're not, is what we're saying to media.
That's one way you can find what we're doing. It's one of the best ways. Another great way is through our website web podcast will Kill You dot Com. On our website, you can find all sorts of things like transcripts. You can find the sources for each and every one of our episodes. You can find a first hand account form, you can find a contact us form, other things. That's all i'm gonna say. Well, links to Patreon and merch and other things.
All kinds of things. Thank you for rating, reviewing, and subscribing on your favorite podcatcher or on you Tube. If you're watching this, yes we're hearing the exactly right studios. Thank you to everyone. Thank you working right now.
This is the longest intro of all time.
Are we done yet? Yes?
Okay, great, we're done. Let's take a break. Okay, and then and then get in get into it.
Thanks great.
Bye.
My name is Amanda. In twenty nineteen, at fifty two, I was diagnosed with stage three triple negative breast cancer. The diagnosis was a shock, not only because of its severity, but because I truly believed I was doing everything right. For years, I followed a clean alternative wellness lifestyle. I it organic, avoided plastics, used non toxic products, took supplements, exercise regularly, maintained a healthy weight on a low carb diet,
and didn't smoke. One pivotal decision was replacing annual mammograms with thermal imaging. Felt empowering in hindsight, it was a serious mistake. When I found a lump in my left breast, I turned to thermal imaging. The scan came back low risk for cancer. The practitioner diagnosed it as a cyst, suggested rebounding exercises and cost oil robes, and confidently told me it was far too large to be cancer. That reassurance was dangerously wrong. The lump didn't shrink, It grew
quickly and painfully. When I finally saw a breast radiologist to aspirate what I believed was a cyst. My cancer journey began. I was thrust into aggressive treatment because my cancer demanded it. I underwent six cycles of chemotherapy, including the so called Red Devil. I tolerated it well and the results were remarkable. The tumor disappeared completely. Surgery followed, first to lumpectomy, then a unilateral mistectomy due to residial disease.
Losing my breast was and remains a profound loss. I still wondered whether the earlier medical or intervention might have changed that outcome. Radiation and oral chemotherapy followed during South Africa's COVID lockdown. The treatments were challenging, but manageable cancer forced me to re evaluate everything I thought I knew about health. Over time, I stopped trusting methods that offered certainty without evidence, and learned to hold space for both
intuition and science. My version of health today is far less rigid, less fear based, and more informed. I have seen how vulnerable people are to misinformation, wrapped in hope and sold as wellness. And if there's one message I hope people take from my story is that there's strength in questioning our beliefs and in choosing evidence based care.
Hi. My name is mccannaugh Elvin ORMMBT, Florida, and when I was fifteen years old, I was diagnosed with stage three uing circoma aware from my bone cancer. My aud's survival were about fifty thirfty. I underwent countless runs a chemotherapy and had a serious to remove my left fibula. Because of how aggressive the type of cancer I had was, cancer immediately became my entire life. I was pulled from school and spent most of my time in the hospital.
It felt like I didn't exist outside of my disease. There was also just this chance I wasn't going to Chemotherapy is also pretty violent in nature. It felt like every part of me had to be stripped away in order to get rid of the tumor. I lost my hair, my tone as will turn black and fall off. I had horrible mouse words that kept me from eating. I had chronic insomnia. Felt like I kept giving and giving until by the end I was just a shadow of
a person with really only my life left. I ended up responding well to treatment, though, and I was able to go back to school for my senior year of high school.
Two years after my initial diagnosis.
At first, I was excited to go back and built it'd be a new chapter for me, we where I'd be a normal kid again. Instead, I began a whole different type of suffering. Sitting in a desk, I felt like I didn't know how to exist as a person anymore. I'd gone from being fifteen so coming into my own to cancer becoming my entire life. I now couldn't claim the cancer identity, but also physically and mentally, I didn't
resemble the person I was before. Looking in the mirror, I followed disassociation to that person and couldn't grasp who I was the same time I was suffering from PTSD, I was continuously having panic attacks and took myself to the emergency room on a couple of different occasions, convinced my cancer had returned and I was going not to start the process all over again. I ended up becoming severely depressed and got to the point where I really didn't want to be alive anymore, which brought on a
deep survivor's guilt for even having these feelings. People weren't very understanding of. This ended up being a really isolating and lonely time in my life, and I just wish someone had told me that what I was feeling was completely normal. One in five people ended up with PTSD after cancer treatment. It took me years to find a sense of self and peace again. This past July was my ten years cancer free. I'm eternally grateful for all the moments and experiences and things I've been able to
accomplish since I was at fifteen year old. I am truly so happy for my life. But I also want to go back to tell myself that what I was feeling was okay. I didn't need to feel grateful for something that should have never happened in the first place. No matter what, I was always deserving of my life.
Forty percent of us will develop cancer at some point in our lives. Seventeen percent of us will die from cancer.
Gosh, those are such sobering statistics, Aaron.
Really, yeah, I know the number of times I double checked it and was like, confirm other sources. Is this right? It is? And again you know these are estimates, they are not destinies. Our knowledge is always evolving, treatments are always improving, We're putting more fun into prevention and so we might see those numbers shift in the upcoming decades or for future generations. And neither are these numbers globally consistent.
You know, diagnosis, access to treatments, and screening, and demographics vary dramatically across countries. But no matter how much you hedge or qualify these estimates with well technically, the undeniable reality is that cancer is extremely common and quite deadly. Why Why Why? That one word question has inspired countless research articles, medical foundations, textbooks, hospitals, memoirs, documentaries, podcasts. It
has shaped lives, careers, relationships, perspectives. It holds the key to understanding not just this disease, but multicellular life itself. Over these four episodes, we might not fully answer this question of why why, Yeah, but we are going to explore many different aspects, many dimensions of it, like why cancer is so prevalent, why it's so challenging to treat and prevent, why each cancer is unique, and why despite all these whys, we should still be optimistic about the
future of cancer research. I like that part, yeah, But before we approach any of these individual questions, we need to start at the beginning. What is cancer?
What is cancer.
Drawing the bounds around what cancer is and what it isn't is trickier than it sounds like. Just ask our immune systems, and those boundaries have changed substantially over history, and so for my part of this first episode, I'm going to explore how our understanding of cancer has changed over time and how that has influenced the noise or the silence surrounding it.
Okay, okay.
In the early decades of the twentieth century, after the dust had settled from that vaccines, pasturization, sanitation and a septic technique and antibiotics, much of the world was surprised to find that a health revolution had taken place. Infectious disease, which had for millennia made an early, gravely expected norm,
no longer held the power that it once held. Children drinking pasteurized milk and vaccinated against smallpox could now more reliably expect to live long enough to experience the joys and disappointments of adulthood, and adults drinking clean water and operated on by a surgeon with a clean blade were now more likely to feel the mixed blessing that came with the aches and ailments of old age.
Well this is so interesting already, Aaron like, I just okay, keep going, keep going. I just want to know more.
Is this cliffhanger? Yeah, you're just like, what is something on the horizon?
It's cancer.
It's cancer. Yeah. As infectious disease stole less of the spotlight, other diseases became more visible. We've talked about this phenomenon many times on the podcast, and among these diseases is cancer. Cancer was not a new disease, of course, but at the beginning of the twentieth century, cancer was not even in the top five leading causes of death in the United States. Really. Yeah, it was eighth on the list. Wow.
Yeah, sorry, remind me of the year because my brain is.
Like nineteen hundred okay, yeah, yeah, not even in the top not even in the top five. Wow.
Okay.
Life expectancy was forty nine years wow, which is a flawed metric. It doesn't take into account the effect that of infant and childhood mortality would have on those numbers, which was primarily from infectious disease. But overall, people were not living as long as they do today, and cancer was less prevalent, partly because people were dying before developing cancer.
Cancer happens to be a disease later in life. Life most commonly partly because our relative lack of knowledge about cancer meant that many people had cancer but never realized it, and partly because certain cancer risk factors, such as smoking, were lower than in the following decades. Okay, So, for instance, at the turn of the century, a case of lung cancer was rare enough to point out to med students so that they saw it at least once in their careers.
Really, that's depressing.
Yeah, over the first half of the twentieth century, all that would change. Yeah, all of it.
That's quite actually particularly disappointing with regards to lung cancer because we're people just not smoking. We need to do tobacco as like an actual episode Aarin.
I have that written in here multiple times. Yeah, there are some really interesting trends about like smoking, and of course it's very different country to country and by age group and stuff like that. But yeah, I mean cigarettes were really became popular, especially after the World Wars.
Got it, ok Okay, that makes sense.
Over the course the twentieth century, life expectancy rose. Cancer research began to shed light on the disease, so that more cancers were diagnosed and then lumped into this rapidly growing umbrella term of cancer. And certain cancers increased in incidents as exposure to carcinogens increased, like with lung cancer and cigarettes. Even though cancer was not a new disease, even though this rise was driven primarily by growing awareness and life expectancy, cancer became labeled as a disease of
the twentieth century. It represented corruption, consumerism and excess, the uncontrolled population growth happening within cities, the danger of nonconformity, oh, and the threat of invasion.
Okay, yeah wow.
While microbiology had demystified many long feared infectious diseases, cancer remained one big question mark that scientists could not answer. If cancer cells were part of us, why were they harmful? Why did cancer strike one person but not another? Why does cancer happen at all? Science couldn't yet provide any satisfying answers to these questions, and so people did what
they so often do, They invented their own. Broadly speaking, the explanations, or rather blame, really fell into two main categories, modern civilization or yourself. Of course, you are to blame.
It's your fault. It's your fault.
Yeah. Throughout much of the late eighteen hundreds and into the nineteen seventies, really all the way through that whole time, that vast amount of time, people diagnosed with cancer were told that they had brought it on themselves by bottling up their feelings, that it was the result of depression, and a quote unquote cancer prone personality type was constructed.
Is this just Freud who was diagnosing cancer?
No, oh my god, this was this is before Freud, after Freud. I can't blame Freud for this. I know, it's too bad. We do like to do that, we do. I'm sure he had a hand in it.
He was a proponent.
Yeah, yeah, yeah. So in her book Illness as Metaphor, Susan Sontag describes this cancer prone personality type quote the forlorn, self hating, emotionally inert creature. She had been diagnosed with cancer, and so this is what a lot of people would That's like how you were talked about, like, oh, well,
this creature, this creature. Yeah. At that point, So this Illness as Metaphor came out in nineteen seventy seven, and at that point cancer had been a subject of intense scientific scrutiny for decades, and yet this blame language persisted. People are afraid of what they don't understand, and our understanding of cancer is relatively new, incomplete, and constantly evolving. That imperfect knowledge has resulted in blame. It has resulted in fear, and it has resulted in silence and euphemisms.
When Ulysses S. Grant developed throat cancer in eighteen eighty four, his doctor acknowledged that cigars they might have been to blame, but added that quote depression and distress of mind was a more important factor end quote.
In the development of throat cancer. Okay, yeah.
Obituaries in the early twentieth century alluded to quote unquote lingering illness as the cause of death rather than print the word cancer.
Really, so they don't want to call it cancer.
They don't want to call it cancer. And then even when the taboo on cancer kind of lifted and there was an outcry for more research, there were there was like an organization that was like, oh, we want to meet to talk about breast cancer, and they were like, we can't print that.
Okay, yeah, great, great, great great, yeah cool.
When cancer was mentioned during that period, it was often in like lurid terms, like Senator Matthew Neely used in nineteen twenty eight during a speech demanding funds for cancer research. Quote, I proposed to speak a monster that is more insatiable than the guillotine. It has prayed and still praise upon every nation. It has fed and feasted and fattened on the flesh and blood and brains and bones of men and women and children in every land. The name of
this loathsome deadly and insatiate monster is cancer. End quote.
So interesting, Aaron to go back and look at these kinds of ways that we describe cancer and like compare that to what how we fighting against cancer today?
Oh?
Yeah, I mean there are there are entire books written about like the language that we use when we talk about cancer. And you know, more recently or since since the nineteen seventies, I guess the language is much more likely to be military code of yes, right, the war on cancer and all out of tack, defeating the enemy, and aggressive aggressive, aggressive aggressive, And that shift to this military language, it has not eradicated victim blaming, which can
come in more indirect ways. Right, you know, healthy mind, healthy body, The implication that cancer will defeat you if you don't fight hard enough.
Yes.
And also I think there's this tendency that we all have. I think it's human of us that when we hear that someone has cancer, we want to know what kind of cancer is it?
Oh?
Were they a smoker? So that we try to find ourselves in that well, well we won't be that won't happen to us.
Trying to understand I didn't do this, what was different about you? What's different about me? Why does this not.
A Why do I want to make sense of this diagnosis? And I want to I don't want this to happen to me. Yeah, And so we try to find that reason. We try to find a cause and effect.
Yeah.
And today the fear of cancer and the blame is as real and as palpable as ever. Surveys looking at fear of chronic diseases show that people fear cancer more than any other chronic disease, even though heart disease kills warm people one killer.
That's actually really interesting. I did not know that, Aaron. That doesn't surprise me at all, No, because it's the thing I mean, I know, like when you have if you're concerned about it, everyone wants to tiptoe around do we even say that we're concerned about cancer? Or do we not even say the word cancer yet? Kind of thing that still happens in medicine todays.
Yeah, I mean that's a whole I know, I have a lot of I know, I know, but yeah, I mean, why, Like, what is it about cancer that elicits such dread? And I don't think that it's an unreasonable fear? Yeah, I would not say it at all. I'm I have that fear. Forty percent of us will develop cancer at some point in our lives. But what that looks like or when it might happen, we have no idea. It could mean a diagnosis in childhood, in middle age, or later in our lives, all of the above, all of the above.
It could mean a simple curative surgery or a marathon of expensive and tortuous treatments. It could mean delayed plans, canceled plans, or new plans. It could mean becoming a caretaker or being taken care of. It could mean hope, despair, clarity, a new knowing. It could mean every one of those things, some of those things, or none of those things. Cancer is unpredictable by nature, which is part of why it
inspires such fear. It has touched every one of us, ourselves directly or through our family, our friends, our neighbors, our colleagues. But we can't necessarily look to others' experiences to predict how our own story will unfold. We want answers, what's my prognosis, will this treatment work, how long do I have? What side effects will I experience? What happens next? But most answers are best guesses, formed by decades of research and always qualified with it's likely that, but we
can't know for certain. And that doesn't represent a failure on the part of the research community, which has produced a true wealth of information when it comes to cancer, what it is and how to treat it. Will more research helped to fill in those knowledge gaps and shorten those error bars in some situations. Yes, but the fact remains that cancer is so unpredictable because it is so variable. Cancer has many causes, many origins, many pathways, many outcomes,
and each cancer is distinct. And I don't mean that breast cancer is just distinct from prostate cancer. Each individual case of breast cancer is unique and as we'll discover more next week. When we talk about like the cellular biology of cancer, oftentimes that uniqueness goes all the way down to the cellular level, with tumors made up of a diversity of cancer cells. The more we've discovered about cancer,
the bigger this term gets. So let's go back to the beginning and see if we can trace its growth over time, just like.
A cancer cell.
Sure, cancer might be a defining disease of our time, but that doesn't mean it's only of our time. Fossil remains of humans and our hominid relatives show us that cancer has been a part of us for millennia and beyond.
Forever and ever forever.
A million year old jaw bone found in East Africa with evidence of lymphoma A million.
Yeah, wow, Yeah, what kind of jow bone?
What like a homind job? Sorry? I was like, no, I don't think I wrote the species down because I think it was like, we're not really sure anyway.
Wow, fascinating but yes, okay.
A growth in a Neanderthal skeleton from one hundred and twenty thousand years ago. An ancient Egyptian mummy from four hundred CE with abdominal cancer and that's just to name a few. I literally cut out so many more examples where I was like, there are papers, find them in our show.
Lots of examples.
Yeah, but looking beyond present absence to prevalence, cancer does seem more common today than in centuries or millennia past. And that's due to the mix of factors that I already mentioned. But it's kind of hard to be more specific than that, like how much more prevalent considering that cancer doesn't always leave its mark on bone, and that we've you know, we've examined only a tiny fraction of the fossils or remains that have been left behind. Yeah, okay,
so what about the written record? Oh so, starting in ancient Egypt, naturally, we've got the Edwin Smith papyrus from about thirty six hundred years ago, which describes what sounds like a case of breast cancer. This is paraphrasing a little bit quote. If you put your hand upon his breast, upon those tumors, and you find them very cool, there being no fever at all. They have no granulation, they form no fluid, they do not generate secretions of fluid, and they are bulging to your hand.
End quote, Okay, yeah, could be, could be, could be, could be.
Yeah. And although this papyrus contains many remedies for all the other ailments that it has listed in there, there is no treatment for this disease. Interesting basically says there's nothing. Yeah. So following this, there was a relatively long period of silence when it comes to writings about cancer, until we get to ancient Greece, where cancer again makes an appearance. Not in a medical context this time though, but a
storytelling one. So the Greek historian Herodotus, writing around four hundred and forty BCE, briefly tells the story of Atosa, the queen of Persia, who developed a swelling on her breast and ultimately headed excised. Was it cancer? Was it an ulcer or fiber adnoma?
Yeah, lots of benign tumors.
We don't know, We don't know. And it's in the Hippocratic texts written in Greece in the fourth and fifth centuries BCE, which I still have to look up every time, Like if I were to go to trivia and that was one of the questions, I would not know. But this in the Hippocratic text is when we first find the words for cancer and carcinoma or their origins.
Okay, that's that was gonna be one of my big questions. Yeah, so that's a long time ago, time ago.
So carkinos, carcinos, and carcinoma.
Okay with ks.
Carcunose was used to refer to any non healing, swelling or ulcerous formation, including things like hemorrhoids or cysts. Okay, interesting, while carcunoma was generally reserved for a non healing growth.
Okay, yeah, non healing growth. This is so interesting.
M Both words come from the ancient Greek for crab. Ah, this is where crab comes from. Okay, So apparently the appearance of a tumor surrounded by blood vessels branching out reminded Hippocrates and then later Galen of a crab in sand with its legs all spread out.
Interesting. Yeah, so that's how they Okay.
Yeah. Hippocrates also used the word methistemi for metastasis.
Oh.
Interesting.
Methisdemi means to remove or set free, and he thought that quote metastatic affectation are those which travel from one to another part of the body.
Yeah, end quote.
It's not wrong, Yes, I mean he's not wrong. I don't think that, like, I mean, given sort of the leading ideas about disease, right, his word, the hit metastasist to him is not the same metastasist to us. But it is interesting, yeah, the roots of that.
Yeah.
Yeah. So then after Hippocrates we run into Galen, whose humoral explanation of cancer dominated Western medicine for centuries, a build up of black bile, also known as melancholy.
Oh that's interesting. Yeah, that that's just persistent without people probably realizing they were doing that. But so sorry, so they were like, cancer is black bile. That's the that's the that's there. Yeah, done, done, okay, Yeah. God must be nice just to have an explanation for something, huh.
I mean.
We wouldn't know.
No, yeah, we can't all yeah, yeah, yeah we are. That's that's that's how we do it on this podcast. Will kill you. But so yeah, according to Galen, I mean, what you can what you can do with black bile is you can maybe like drain a little bit of it, but it's really difficult to do. Also black so black bile is melancholy, and it's like depression and repeat.
I don't know about this in your which episode was that that you did all of the humors ball bladder? And we were like, what is black bile?
No, so, I mean I didn't put this in here, but like this is like and black bile not just specific any of the humors, right, people knew what blood, people knew whatever, slam, but black bile was this mysterious thing that no one could find. And then I think it was like visalias. I hope that's right, was trying to find he was trying to like confirm Galen's black bile and the humoral theory and was like doing auto and he was like, I don't find anything where it is.
What is this?
And so it was kind of like the beginning of the end which had already been under question. Blah blah blah blah. Medicine was not stagnant for that long, et cetera. So but Galen for the most part was like, I don't think that we should treat this. I don't think that surgery is the way to go. It's only going to speed up progression. And so unless it was like very small, he tended to opt to just do nothing, okay,
And later physicians kind of did the same thing. It was very much like some did surgery, some didn't, and many other many other, many other surgeons physicians contributed to this body of knowledge about cancer, but like it was incremental and none of it really moved the needle, yeah, in terms of like what does this do for the patient? Right, or even like our understanding to then try to develop something.
And so even though so Galen's black bile concept of cancer came uter scrutiny as early as the fourteenth century, it overstayd It's welcome, though for much much longer than that, no central hypothesis of cancer took its place, and physicians remained largely helpless to treat or even just understand this disease of many faces. That's so interesting, And things started
to change around the eighteenth and nineteenth centuries. Okay, all right, So science and medicine during this period is marked by the invention of tools and techniques that allowed physicians and scientists to observe for themselves what had previously been invisible.
The thermometer that indicated a fever, the stethoscope that detected a heart murmur, the microscope that revealed the cells that formed us and all of life, the taboo against autopsies had been declining for a couple of centuries, which allowed people to map out not only how the body worked, but also like when things went awry. With this new toolkit, patients were more likely to find confirmation and explanation of
their vague symptoms. Surgery back on the rise, especially once antiseptic technique and anesthesia were introduced in the later half of the nineteenth century. Surgery revealed that the exhaustion and the aches that you had been feeling were likely tied to the tumor in your breast that had spread to your bone. A slide of your blood cells viewed under the microscope pointed towards a proliferation of white blood cells as a contributor to the listlessness and abdominal pain you
had been experiencing. As a medical topic, cancer was not unknown to the physicians of this era, but it evaded explanation. These new tools surgery, microscope, anatomy, chemistry gave them the opportunity to pin down this disease, focusing on two main questions, what is cancer and why does it happen?
This is so interesting erin because I don't think that I expected for there to be a kind of unified idea that cancer is cancer from that far back, like I thought that this was going to be you being like and then they thought that this was some weird disease and it turned out that was also cancer.
Like, yes, that is kind of what it. I mean, this is things are still coal.
Yeah.
So it's just like now we have in the starting in the nineteenth century, we have these tools, we have this idea of like, Okay, now we're going to throw out this black bile theory which had been around for a really long time and kind of lingers still, and we're going to kind of see like what this individual one is. And so breast cancer was still viewed as a distinct thing. Okay, and it is, I mean, and you can see why because like there are commonalities between
some and not between others. Yeah, exactly so. But it's what happens now. The story I'm about to tell you is how we form the idea of cancer itself, like the mechanism, the recognition of it.
Especially because you're like blood cancers versus solid tumors like this, they all can look so different.
They all can look so different. So how do we come up with cancer?
Cancer okay, okay.
In eighteen forty five, German physician Rudolph Virchow aka the father of modern pathology, published a case report on a fifty year old woman who had been admitted to the hospital with edema in her legs, a swollen spleen, diarrhea, and nose bleeds. Okay, she was treated according to the standard of the day, which was like leeches, bleeding, purgatives,
et cetera, but she passed away. Three months later. Virtue conducted an autopsy and found that some of her organs were teeming with white blood cells, with hardly a red blood cell to be found. Yeah, and it was like, like he noted that it was like the normal ratio of white blood cells to red blood cells had just been reversed, and it was like the white blood cells were so they were so numerous that they were preventing
the production of red blood cells. So to Virtue, he was like, Okay, I've seen many white blood cells before in like, you know, infections, but this doesn't look like that. This is not like the thick you know, pus whatever yellowish that happens after an injury or a festering wound. It's just too many white blood cells that looked slightly off. They looked mostly like normal white blood cells, but they were not a little bit off, And so he gave it a name, leukemia.
He named it.
He named it. It's Greek for white blood. Yeah, yeah. And this name is was revelatory because it didn't imply a process or a cause. It simply described what he saw interesting white blood. And over the following years, Virtue continued to examine and describe cases of leukemia as well as solid tumors, and he found a common thread. Uncontrolled cell proliferation seemed to be at the root too, many of whatever type of cells a little bit odd, okay, yeah, okay.
And so since our bodies are made up entirely of cells, which was kind of a relatively new concept at the time, like cell theory had really just formalized in the early eighteen hundreds, like eighteen thirties, Yeah, then that meant that these malignant growths could start anywhere within our bodies neoplasia which is what he called it, also, and that cancerous
cells could travel anywhere throughout our bodies. Virtua's framework of uncontrolled cell proliferation, articulated in the mid nineteenth century became the leading concept of cancer. It displaced the plethora of vague, non mechanistic hypotheses like it's a buildup of lymph, or it's poisons from the soil, or it's an excess of black bile. And it still really provides the foundation for
our current understanding of this disease. It didn't explain why cancer happened, but it gave people an image to search for and a way to diagnose. Just too many of one thing and it's a little bit odd.
Yeah.
With this, the field of cancer research had broken open. Three primary, though overlapping avenues emerged. Mechanism, what's causing this, epidemiology, who's getting it? And treatment? What do we do about it? And Since at least the late seventeen hundreds, scientists had identified patterns of cancer and populations, whether through environmental or occupational exposure, like scrotal cancer and young chimney sweeps. Huh, you don't know this story, Okay, wait for the fourth episode.
I cannot wait. It's great or familial clusters like Pierre Broca's research on hereditary breast cancer, but these proved to be exceptions. In the majority of cases, there was no family history or known or distinct environmental exposure. So the other big scientific and medical revolution at the time, microbiology wasn't providing many answers either. While different fevers began to be divvied up among different bacterial pathogens or microbes, they didn't seem to be at the root of cancer, at
least not obviously. So it was our own selves causing the problem, Just as Virtue observed in the late eighteen hundreds and early nineteen hundred, it's improved microscopes and staining techniques began to shed light on what it was about our cells that was causing these issues. They look slightly off, but what is that offness?
Right?
What is off about them?
Yeah? Yeah, our chromosomes was one thing that they observed. Basically, something happens to the genetic markup of a cancer cell that causes it to replicate uncontrollably, and the resulting cells inherit that faulty genetic material, continuing this pathological cycle of growth and metastasis. So this is when they started to also realize that not only are we all made up of cells, but that each cell then divides and creates more cells, and then what is what are the instructions
that are inherited chromosomes. If it's inheriting faulty chromosomes.
Then it's going to be a faulty cell yep.
Yeah, yeah, this is how cancer grows.
Right, Yeah, what a time in research, My goodness.
But like, still, what was the initial trigger? What happened to at the beginning to then lead to that abnormal chromosomes? There didn't seem to be a consistent answer. There was radiation in cancer, chimney soot and cancer cancer that ran in families. But these diverse explanations were unsatisfying. How is it possible that these disparate things were all resulting in the same disease process? How then a beacon of hope. In nineteen ten, Peyton Rouse discovered that he could transmit
cancer from one chicken to another. Oh yes. The discovery of the Rouse sarcoma virus, which is the first cancer virus to be discovered, kicked off a frenzy of research. Maybe there's a virus for every cancer if we just look hard.
Enough, just look and find it.
And for some time that seemed like it might pan out. There was the chop Peppelloma virus was identified in nineteen thirty three, which is that cancer causing viruses that causes tumors and rabbits. We talk about it all the time in our talks, but it may have led to the jacalobe myths, these likeny growths.
Yeah, rabbits.
There were mouse viruses that caused cancer, cat viruses, and the first human cancer virus to epstein bar virus associated with Burkett's lymphoma, that was described in nineteen sixty four, and so over these decades, Over this fifty years or so, a handful of people were still working on environmental and hereditary causes of cancer, but the majority of research funds for basic cancer biology, which was a smaller portion of the pie overall for cancer funding, was geared towards this
viral hypothesis of cancer sting.
Yeah, that's really really interesting to think about.
Right, And given the huge strides made in the first half of the twentieth century when it came to the control and prevention of infectious diseases, especially when it came to vaccines, it makes sense that viruses were an appealing answer to the question of why does cancer happen? Because if you could just come up with a vaccine.
Then then that's it. Then we can be done with it.
It can be done. Yeah, well yeah, there's still you know, you can get people to take the public buy in and all of that. Yes, But after decades of research, it became increasingly clear that viruses held the answer in only a small proportion of cancers, about ten to twenty percent, and by the mid nineteen seventies, research took on a more balanced approach, also investigating environmental and hereditary causes of cancer.
But that era of research where like the viral hypothesis ruled all people were also had other people were like yeah, I know, sorry, hedging hed hedgelah. But it led to the discovery of oncogenes. And this is a really fascinating story which you should find out, but it's too long to include here. But these onco genes essentially in trying to find out what it was about this virus that
led to cancer, of what were they doing to charge themselves. Yeah, they were like, there's this different version of a gene that's causing it's like a mutated version of a gene that we have, but it's causing the cell to proliferate with no often keep growing, just go go go go go. Yeah, and so onco genes and then later tumor suppressor genes. That the finding of these you know, mutated forms of normal genes that then either you know, gas pedal to the floor or the brake is broken.
Yeah.
Yeah, they helped to unite the three main drivers thought to cause cancer. Right, there's environmental, viral, and genetic, and so an environmental exposure could cause mutation in a normal gene, turning it into an oncogene. Right, gas to the floor. A virus could insert its oncogene into the host cell's genome. Gas to the floor. Someone could inherit a predisposition where oncogene development is more likely, or they inherit faulty tumor suppressor genes either gas to the floor or no break.
And we'll talk about those. Talks are about those. Yeah.
So this is how this unifying. Okay, cancer is this thing that can happen through many different roots.
All these different mechanisms, same end result.
Same end results. Yeah, yep. But so many questions remained. How do these mutations happen, what are the pathways? How predictable is this process? What are the genes are involved? Can we harness any of this information to prevent or
treat cancer. Up through the nineteen seventies, research on cancer biology and cancer treatment was happening almost entirely separately, really really okay, So even at a cancer conference you wouldn't really find like a cancer geneticist attending a clinical oncologist talk and vice versa. Just wasn't really something that could
and very siloed. And after the initial promise that chemotherapy had shown more on that in the third episode, clinical oncologists grew frustrated as they discovered that what worked for one type of cancer, or even just one person's case, you know, did work for another. This dream of a magic bullet for cancer was slipping out of reach. Cancer biologists validated this with their research as genetic sequencing revealed the complex and unique pathways that drove each individual cancer
and how those pathways evolved over time. And so when Nixon announced the War on Cancer in nineteen seventy one, it was useful. It was really quite useful from a funding an awareness viewpoint. It was like, you know what, this is a thing. We're going to fight this, this is a priority. This is a priority. We are going to Cancer is an.
Under fund it the way that we fund war.
That is the idea. That was the idea, Yeah, but it also had the effect of distilling this incredibly diverse process into one disease with one mechanism, one pathway, and thus one mythical cure. And when that cure failed to materialize,
the public grew disillusioned. There was the sense that if we could just form a task force, we could just task force our way through this, just throw enough resources and expertise at this problem, then we could come up with a solution in no time, because this is what the Manhattan Project had done during World War Two, right, Like,
why can't we just do this? But reality didn't quite align with these high expectations, and in nineteen ninety seven, a controversial study came out in the New England Journal of Medicine with the jarring title Cancer Undefeated. So this was about, you know, twenty five, twenty six years after Nixon's War on cancer. What was inside was even more shocking. The report demonstrated that from nineteen seventy to nineteen ninety four, cancer deaths had either plateaued or increased for most cancers.
In the few cases where cancer mortality had declined, it was mostly attributed to screening and prevention. The paper was criticized, reasonably so, because it seemed to call into question the decades of cancer research and the millions in cancer funding. Friend it showed was real cancer remained deadly. But what it didn't articulate were two very important things about cancer. Number One, cancer is not one disease, but many. A paper like that falls into the same trap of coalescing,
this distilling into one thing. It shaves off all of the nuance, any of the color around this thing. So lumping all cancers together does not allow us to see the nuance where substantial progress has absolutely been made or where we still have a ways to go. And number two, the other thing that it didn't really articulate about cancer was that cancer is a disease years in the making, both in terms of its pathology as well as our understanding.
The cigarettes that you smoked in your youth might lead to cancer decades later, just as the cancer biology we're uncovering now will give us insights into treatment that will take years to develop, tests, approve, and become a standard of care.
I think that's one of the hardest things about how fast things feel like they're moving right now now is that they still aren't fast enough for people today? You know, and they are reality.
It is, it is yeah, and you know these it will take a while for these things, these headlines to actually become reality that people can access if you know, there are other issues with access and but for some treatments it has already happened. Some cancers have been completely transformed because of our understanding and treatment development. Over its history, cancer has been assigned so many meanings and definitions. It's been a disease of black bile, a cellular pathology, a monster,
a genetic mutation, an enemy, a curse. In cancer's metaphors, we see the fear and the blame that is so human of us. In our narratives of cancer history, we may emphasize scientific progress over failure, and in our personal stories of cancer, we may assign villains and heroes, cause and effect. We want cancer to be one thing, but it isn't. It has many causes, many mechanisms, many pathways, many beginnings, and many endings. Each time we try to
draw hard boundaries around it, cancer resists them. It demands that we look again and reconsider, and when we do, we find something that for me has been perspective shifting. We find that the same cellular mechanisms that allow a cancer to proliferate and metastasize are those that underlie our ability to heal wounds or develop from infancy into adulthood. Yep, we find ourselves. We find what it is to be a multicellular being. Cancer is not a failure of ourselves.
It is a consequence of multicellular life. To understand why cancer arises in the first place and why it's so difficult to prevent and treat, we have to explore cancer in an evolutionary framework. Yes we do, which is what we'll be doing next week. But before we get there, I'll actually have to define, like what cancer is?
What is it today?
Today? So, Aaron, what is cancer?
I would love to tell you what I can.
Hi. My name is Kara Ringstorf. I was diagnosed with stage four colon cancer in late twenty twenty four, right before my thirty third birthday. I had been experiencing blood in my stool for a few years, and around three to four doctors dismissed it as fishers or like hemorrhoids. I was very anemic at one point and was sent to an oncologist who was also a blood specialist, and he told me I was just like knemic because I
was a menstruating female. About a year and a half later, it am like there was more blood, so I told my primary care physician that I wanted a specialist. I had my colonoscopy and they found a four centimeter tumor in my sigmoid colon. So I had my sigmoid colon reception pretty soon after, and while I was in recovery, they biopsied my liver and it turns out it had metastasized to my liver, meaning I was Stage four. About
a month later, I had my first round of chemo. Unfortunately, the pump they sent me home with with the five FU, which is what my treatment plan was, gave me a stress induced heart attack, which only happens about one to two percent of patients. So I started back up and switched chemo to a different schedule than what the traditional five FU regiment is, and a couple of weeks later, I had a liverysection in early March of twenty twenty five,
so now I'm in remission. Since then, I have of sea tea scans and blood work done every three months. I know that I'm in mr mission, but also with the reoccurrence rate and everything, it still kind of feels like a death sentence for me.
Hi. My name is Rachel, and today I would like to share my twin sister, Leslie's story. We had a standard sibling relationship growing up and she was my best friend as we entered into early adulthood. The summer we turned twenty one, she was diagnosed with uvula melanoma, a rare tumor growing in her eye. She had almost none of the risk factors, was young, healthy, and active, but
cancer doesn't care about those things. Initial treatment included radiation black therapy to kill the blood supply and shrink the tumor, and she had successful treatment. We were thankful to live in an area with access to excellent medical care, including her ophthalmologist, doctor Oliver. Follow Up included yearly scans that she went to diligently. Leslie went on to graduate with her Bachelor of Science and Kinesiology and health promotion, and
she became a doctor or physical therapy. She got married and lived life to the fulls for the next ten years. In her free time, she loved skiing and hiking, which are typical of a Colorado native. For skiing, she gravitated towards the most technical runs like Christmas Tree Bowl and Steamboat. For hikings, she also gravitated towards technical routes and was able to summit over forty of Colorado's fourteen ers, including some of the most challenging Class four routes like Beer Peak.
I haven't summitted nearly that many, but she, my dad, and her husband slowly kept knocking peak after Peak off the list. Then shortly after our thirty first birthday, she had her son, and in early summer, the unimaginable happened, and she was diagnosed with metastatic y vi la melanoma in her liver after having a clear scan the fall prior. While doctors were again able to act quickly, the cancer was growing too rapidly for successful treatment, and she passed
away less than eight weeks after this diagnosis. I just celebrated my seventh birthday without her, surrounded by family skiing in the mountains. Her husband has since remarried, and I am thankful her son has a mother to grow up with. I'm now a mom to three, including a set of twins. There's no roadmap to grief, and I've learned a lot about giving others grace and understanding because we don't know
what they might be working through. I also think of friends and family navigating their own journeys with cancer, and as a biomedical engineer, I use my sister's story as motivation to continue to engineer medical devices that allow surgeons to have better patient outcomes. I'm also choosing to live life to the fullest, just like Leslie, and I'm thankful to have a supportive husband and family. Leslie didn't want
to be defined by her diagnosis. She wanted to be defined by the things she did and the patient she interacted with. She was a wife, mother, sister, daughter, avid skier and hiker, and a doctor. Leslie, I love you and miss you.
So Erin. Obviously, you covered a lot of ground in that history section. Thank you very much. I really enjoyed it. But we do still have quite a bit to cover in terms of what we mean when we talk about cancers today, and so that's what I'm going to try and get into right now. And there are actually quite a number of different definitions depending on what organization you're looking at. But they do all boil down to this same general concept, which is abnormal growth. Right, cancer is
an aberition of some kind. It is abnormal, it's atypical, it's out of control, it's uncontrollable growth in some way. So one technical definition that I will put forth comes from the National Cancer Institute, which says, quote, cancer is a disease in which some of the body's cells grow
uncontrollably and spread to other parts of the body. Now, I just like side note here because some of the definitions of cancer very explicitly say cancer is a group of diseases, which and other definitions say cancer is a disease.
And I just think that that's a really interesting like that that is still something that I wouldn't say is like up for debate, but is just like a part of how we define cancer where some groups are going to define it more as multiple different diseases and some are going to say, like we're lumping all of cancer as one thing, right, with many different pathways and many different like ways that it's going to turn out. Essentially it's interesting, well.
And it's like there's a deliberate choice there, Yes, exactly what does that.
Mean, what does that mean? I also read it really interesting. I'm so off script right now, but I read a really interesting paper from twenty twenty three that was like a we're proposing a new definition for cancer. That was much and it was an int higher paper that was an explanation for their one sentence definition, like word by word, this is why we chose of instead of buy and stuff like that that you would love it.
I would love that.
But they really focused a lot on the evolution concept, which we're going to talk more about next week. But it's a great paper. I'll link to it, please. So the point is the point is that uncontrollable cell growth, yes, that spreads to other parts of our bodies. Okay, just pause and don't ask me any questions, sure, because I will tell you that. A big question that arises when I hear that particular definition is like how why? How? How are cells growing uncontrollably? How are they spreading to
other parts of our body? I'm not going to answer that question this week.
Can I ask a question?
Yeah, but I just want you to know if it's that I won't answer it.
No, No, No, I kind of know some of that.
Yes, I know you do.
But spread spread is that?
So that is obviously that is a big I'll talk a lot about that this week. Yes, Okay, that is a big part of cancer and that I will talk about this week. Okay, spreads to other part is.
A necessary inclusion in that definition. H fascinating.
We'll get there, we'll get there. But the question of how this happens is what I'm going to focus more on next week's episode. But this week I'm gonna just kind of take for granted that we all understand the idea of a cancer because we've known someone who has
had cancer, et cetera. And what I want to dig a little bit deeper into is what I would call maybe the kind of clinical aspects of how we deal with cancers today, how we define them, how we classify them, and then broad strokes on sort of how we're diagnosing and you know, grouping different kinds of cancers. Okay, and then next week is more the biology of what's happening. Cool.
Great.
So the first way that we have to classify cancers, and I think that we do this kind of almost intuitively when we talk about cancers, is what organ is your cancer coming from? And that is actually the first way that medicine has to classify a cancer too, it's primary side of origin. So where did those cells initially come from? Where they lung cells, where they breast cells, where they liver cells, Where in the body did this
tumor first begin? Oh, I have so many questions already, Okay, okay, And we do this for a lot of different reasons, but it's in part to figure out where it first started. Yeah, and also because pancreatic cancer acts very differently than breast cancer, and so we need to know what we're dealing with, right, which also act differently, by the way, than blood cancers like leukemias and lymphomas. These are all very distinct types
of cancers. Once we have figured out the organ, like the tissue that it came from, that is not the end because not all breast cancers are the same, not all lung cancers are the same. And so the next part that we have to do is figure out what tissue type it came from within that organ.
Okay, what part of the lung?
What part? Yeah, So cancers that come from our epithelial cells, and we've talked a lot about epithelial cells on this podcast, but they're the cells that line all of our body surfaces. So they're like the inside of ducts in your breast. They are the insides of all of our blood vessels. They are the cells that are like lining and making up the inner parts of our body surfaces. These are called carcinomas. And so if you ever hear carcinoma, that
means that it came from epithelial cells. This accounts for like over ninety percent of solid cancers we'll get there, okay, of humans, And you further can divide it from there because there are many different types of epithelial cells. So you might have a squamous cell carcinoma that came from these flat like diski shaped cells, or you might have an adinocarcinoma, which comes from these glandular cells. And some cancers, like breast cancer, for example, most are all adno carcinomas.
But we don't necessarily call them that. We distinct them by did it come from the duct, did it come from the lapule. There's a lot of different types. We get really specific.
Okay, it's wild. I know how many different sub small.
Cell non small cells, squamous cell. I don't know, like there's so many different types of these, even just within the carcinoma category. Aside from that, cancers can also arise from non epithelial tissues, and these would be our connective tissue cancers. Okay, so sarcomas, bone cancers, those kinds of things are called sarcomas, and those are actually a really wide range as well. So for example, a mesothelioma which
listened to our asbestos episode for more detail. But a mesothelioma we think of as a lung cancer, it's not a lung cancer. It's a cancer of the lining of the lung, which is a connective tissue. So even though it gets a special name mesothelioma, it is technically a sarcoma. Whoa, I know, I'm getting technical, but it's fun for me.
I think it well, I mean, I think it's helpful to understand that it truly can arise anywhere anywhere, and the side of origin and the type of origin and blah blah blah all influences the path that the cancer could take.
Exactly, because it all means that these cells initially were acting in one particular way, and so that's going to tell us something about how they might act as they become cancer cells. Then there's also cancers that originate in our bones, like our blood based cancers rather right and bone marrow yes, thank you whoa aaron? So that would be like a leukemias, lymphomas, myelomas, which are all different
types of blood cell cancers. Okay. Then there's also more specific ones you can get like retino blastoma which is in the retina of your eye, glioblastomas which are in your brain, which I think technically might fall under sarcoma, but they're so specialized that there I don't know if they actually technically count as a sarcoma because they again are just so specialized that it's your brain cells. So there's a lot of different ways that we have to
classify it at the beginning. But if we then go back, so knowing that if we go back to our definition of cancer of these cells that are growing in an uncontrolled way, that are then spreading to part of our body, part of this definition is that it's abnormal growth. So what is it that makes these abnormal?
It's a great question, It's a really great question.
And mechanistically we'll get a little bit more into detail on that next week. But one thing to know is that cancers grow in these like disorganized masses, especially when we're talking about solid tumors, right, so everything but the blood cancers, and we call these tumors like that's the name that we call these clumps of cells. But not all tumors are cancer, right. In medicine, we call non cancerous tumors benign. And it's not a great word.
It's not a great word. We talked about this in enemage for you.
We did, yeah, we did, because in medicine, benign does not mean good. It does not mean chill, it doesn't mean don't worry about it. It means that this tumor is not going to metastasize. And that is really the key that makes cancers cancers. It's not just that they're growing these disorganized clumps of cells. It's not just all these things. It's also that they are spreading, and they spread in a lot of different ways. The thing that
makes cancer so deadly is this ability to invade our bodies. First, they're invading past what we would call tissue level barriers, which means that a cancer might start within the duct cells of your breast. But then it's going to invade through the lining of those ducks and into the surrounding tissue, and then it will break off pieces of itself and it will travel whether through your lymph system into your lymph nodes or through your bloodstream to distant organs and
set up shop there. And that is what we call metastases, those little bits of pieces that travel and make new tumors at distant sites.
So, yeah, uh, spread or potential to spread? And what is that quality or characteristic that allows for mobility.
That's a great question. I don't know, Okay, I don't know if we fully understand that.
But like so if you're trying to say, is this a benign growth or a cancerous growth? Yeah, has what how do you distinguish?
That's a great question. They're looking at the We'll talk a lot more about all of the other like cell markers and things that we see on how these cells behave in cancer. Yeah, if that makes sense a little bit next weeks exactly the hallmarks of like how cancer
cells all behave. But and so a lot of it is that it's looking at all of these things, and I think it's also looking at the disorganization of the structure where benign tumors are less likely to be super disorganized, though they might be a little bit disorganized, okay, compared to malignant tumors. So things that are going to be spreading.
And I think too, it's I think that most of these growths now we have well characterized, so we know if you look at this type of tumor, it is not likely to spread, Whereas if you look at this type of tumor, it is likely to spread. And there are some that can sometimes hedge that line where they are not cancerous, but they might have the potential to become cancerous. Okay.
Another question from the class endometriosis.
Oh, I knew you were going to ask. I know, I know, I have to.
I mean, you can find cells anywhere in the body and it can form tishoe, it could grow to shoe anywhere. Yeah, so how is that not it's just as a cancer.
It's no we talked to question. But it's a really good question. And I think honestly, doing this research for this episode made me go back and ask that question myself because I was like, it doesn't kind of make sense. This is one of the biggest hallmarks and it's because the endometrial tissue that we find in endometriosis doesn't meet all of the other hallmarks of cancer. It's not necessarily disorganized,
it's not replicating indefinitely. It's replicating in a way that is in sync with a menstrual cycle and things like that, Like, it's not just going wild. I would say, it's a valid question to think, where is this line blurrier than we think, right? And I think maybe, But I'm just going with what.
I guessh in the boundaries again.
Yeah, Yeah, endometrosis is a wild beast. It is, especially in the context of this. Yeah, because yeah, they spread everywhere. M but that's what cancers do. And because of this, metastases are the reason why. The next step in defining our cancers is figuring out how far it has already spread. And so we do this through a process called cancer staging.
So once someone has a cancer and we know where it came from, we know what kinds of cells it came from, we need to figure out how far it has gone, and so we do this through staging is often called like TNM staging, which I'll tell you what it all stands for. And so first, the first way asterisk on this. But the first way that cancers tend to spread is locally, so from like the inner lining
of your bladder, through the muscle wall or something like that. Okay, So how far a cancer has invaded within the tissue that it's from is the first component of that cancer, and that's the t in the TNM framework.
Okay.
So for example, you could have something called ductyl carcinoma insto, These are cancer cells, but they have not yet left that duct, right, So that's like a stage zero cancer. Okay, same thing with bladder cancer. You might have and this is true for any cancer, but bladder cancer. You might have it that's just within the lining of the bladder and hasn't yet invaded into the muscle. Or you might
have what's considered muscle invasive bladder cancer. So now it's made it through the muscle, Okay, have the bladder wall.
How how much variation is there in terms of like the thickness of these different layers.
Oh that's a great question, huge amounts.
Okay.
Yeah.
You think of like the duct of a breast, Like a breast duct is going to be like a couple sells thick, whereas the lining of your bladder is quite thick.
Right, yeah, And so how does like, does that have any bearing on staging?
It's all I mean, it's all part of the staging process, but like does what does it mean for prognosis and things? That's such a I know, I can't answer that question, I know, I know. So then the next part of
staging is n which stands for node. Because one of the first ways that many cancer spread is via our lymphatic systems, and our lymph system drains into lymph nodes in specific patterns, and so we know, like your breast tissue is going to drain towards a cluster of lymph nodes in your armpit and other you know, your liver is going to train to specific lymph nodes, et cetera.
And so by sampling the lymph nodes in the areas where that original tumor is draining, we can figure out how far the cancer has spread what we consider regionally within the body.
So you would expect to find cancer cells within that lymph node.
Potentially that could be that could be a first place where they may spread.
And is there a possibility that it has spread but not not? No evidence in the lymph node.
Absolutely, because the next step is m from atastases. Okay, because the other way that cancer spread is via the bloodstream, which means they can go anywhere. Very commonly, we see places like the liver or the bones where cancers tend to spread, and part of that is because we have good blood flow to those areas, and also maybe that those are just particularly conducive tissues to grow cancer cells.
Why who knows. But metastases can be literally anywhere. And I said asterisk on the fact that cancers are going to first spread locally. That's not always true. Some cancers have these, especially what we call micrometastases, that might spread very early in the course of disease, and we might not even be able to pick those up if they're
very small. Because the ways that we tend to look for metastatic growth is by doing imaging tests, so that might be CT scans or MRIs or what are called PET scans, and that is to look for evidence of cancer in distant sites, far from that place where we first identify a tumor. Okay, So by using all of this information, we then can stage a cancer. And that's where we think of like was it stage one? Stage two, stage three, stage one, Like you, what stage was your cancer?
They don't all mean the same thing. And there's a lot of nuance to this. So I'm not gonna like get detailed into how we stage these cancers because some get like to ab CD and things like that.
So many very yeah, so many variations.
And especially for some cancers that we have now done a lot more research on and we understand much better, breast cancer as one example, there might be a lot more to staging than just this. There might be testing for hormone receptors. There might be testing for particular antigens that we see on the cancer that we happen to have treatment for so we could then treat it with specific medications. And so there's more to the staging process.
But this is the like broad strokes picture of it that can give us a sense of I won't say prognosis, because that's not quite true. Like it, how bad is this going to be? Is not quite the point of it,
but it's part of it, right. It's being able to group different types of cancers together, both for like clinical speak, to be able to talk to somebody about their cancer and have them understand this framework and also to be able to do clinical trials so that people with similar types of cancers with similar distributions in terms of nodes and metastases and things, are going to be participating in
trials for different medications. And it also, I think creates this language that allows us to say stage four means that your cancer is metastatic, Stage zero means it has not spread outside at all, and everything in between is a lot more gray area.
Sort of like, Okay, how how long has this been going on? How fast did we get here? And where might this go from here?
Kind of except that every cancer moves differently in terms of speed, so not so much on the how fast did we get here necessarily, but like where are we not? Where are we starting from?
Starting from?
And what does that mean for them? What the treatment options are and things like that.
So okay, so let's say that you are you go in because you suspect you have a suspicious growth, and you're like, I want to get this checked out. Yeah, what are the steps for staging? Like what does that look like for someone?
I was hoping that you would ask me that question, Elsetair, because it's like the question is like, how are we
diagnosing cancer, How are we doing this right? And it can start with a really wide range of things, depending on if you come in saying, you know, I have a lump that I'm worried about, or if it's like I've been losing weight and I'm not I'm nauseous, or if it's I'm fatigued, and so like, the how you get exactly to that initial diagnosis can really really vary depending on the type of cancer that we're talking about.
A cervical cancer we might pick up on a pap smear, a breast cancer we might pick up on a mammogram. Something like a blood cancer. You might have to have blood work done and it just be abnormal for someone to be able to recognize that. So there's a huge range of how we get to that initial one. But then the next step is actually a tissue diagnosis, which means getting a biopsy to be able to do all those things we said, where did this come from, what
kind of cells are are they, et cetera. And then the staging process is going to be usually a relatively long process of many, many appointments, but it might include in addition to that biopsy, it might include node biopsies, so, especially for something like breast cancer, you might get node biopsies at the same time that you get an initial biopsy because we know those nodes very well, we know which ones to sample for in what quadrants, et cetera.
For others, it might not. There might not be a nodal biopsy until there's maybe an exploratory surgery or some kind of surgery to remove the cancer, and then you would sample lymph nodes at that same time.
What is it tell me walk me through a node biopsy?
Oh, I mean, I'm not a surgeon or an interventional radiologist, but you are an MD.
So just hoping for some broad strokes subscription.
It depends on It depends on the type of cancer and things. For breast cancer, you could do it without necessarily needing to do like an open surgery or anything. So you might be able to do a lymph node biopsy with just like an in interventional radiology type of procedure. The same thing might be true for a lot of biopsies of things like maybe your liver or even lungs.
You could do with like a broncoscopy. You could do a lot of different biopsies in multiple different ways of both lymph noodes and the tumor itself, whereas for others you might not, like in your guts, it's very hard to sample some of those lymph nodes, and so you might not be able to do a lymph noode biopsy until you're doing a surgery, and then you might take
the whole entire lymph node rather than just us samample. Okay, And there's obviously pros and cons to doing both and right, right, but hopefully that was a good answer.
It was great, Thank you so much.
And then and then after we have all of that, then you're also going to get images tests as well too, and that's to look for distant metastases. And you know, depending on the types of cancer, there could be a lot.
How well does imaging what what is the imaging and then like are there cancers that are missed by imaging or yeah.
Yes, yes, definitely okay, especially I mean, I would say especially micrometastases, Like we're not going to be able to pick up a handful of cells somewhere, right, which is why a lot of times chemotherapy is still recommended. Even if you think we had a surgery, we got good margins we didn't see any metastases. There still might be a recommendation for chemotherapy because we just don't know if there's other cells hanging out locally or more broadly. But yeah,
MRI is sometimes used. CT scans are sometimes used, and then PET scans, which are this like weird and fancy way to look at metabolism.
Basically, it's really cool. It is really cool.
There's still like a mystery for me, but you basically are looking at like glucose uptake and metabolism so that you can see if cells are looking like they're growing more than they ought to.
And you can do fancy scans you can do if you can find specific targeted cell cancer cells exactly. But okay, okay, I just didn't know how well imaging captures.
Yeah, it all just depends like it just depends on the size. And that's why most people with cancer are going to have many scans. It's not going to be just the one. It's going to be that first one for staging, and then they're going to have scans to look for evidence of recurrence or new metastases that we
didn't know about. Because things can change, you know, very rapidly, right, when it comes to how cancer is affecting our body's big picture, most cancer deaths are due to metastasis, meaning because of the way that this cancer has spread through our bodies, and like what is the exact mechanism of that. Who knows, Like it can really really depend. Like it could be that you have metastases to your liver, and so now your liver is failing because it can't function
anymore because it's full of cancer. It could be that you have brain metastases again your brain or your kidney or whatever it is. Sometimes also we can see that, like if tumors grow large or very numerous, they might start to lice themselves or sometimes that can happen as a result of treatment, and that can be very very dangerous because you're basically releasing a bunch of things that are supposed to be inside cells, and that trigger is
a really strong immune response, Yeah, exactly. There's also though, cancer requires a lot from our bodies in terms of our metabolic load, and so it ends up just weakening
our bodies until they really can't function anymore. And so this can result in something called cancer associated cachexia, which is really really awful and it's just this depletion of skeletal muscle mass, especially skeletal muscle mass, that cannot be entirely reversed no matter how much nutritional support you give someone.
And it's ever yeah, it's it's I mean, it's not like no one can recover from this, but you until you get that cancer under control, right right, right, Okay, the cancer itself is doing this, and so you can't completely reverse it.
It's just diverting all the resources.
Exactly. It's exactly that. And it's a very multifactorial thing because a lot of times we do see like people having either food aversions or nausea, whether it's from the medications or from the cancer itself, or if you're talking about like a head of net cancer or an upper GI cancer, you might not be able to eat physically, and so then it's very difficult to get nutrients answers it comes. There's a lot that goes into a kaxia associated with cancer, but that is a really big cause
of death. One estimate that I saw was that cancer associated kakexia accounts for nearly half of all the deaths associated with cancer worldwide, which is which is really huge. And then there's also the fact that cancer dysregulates our immune system in a very profound way, especially when it gets to be metastatic, and so it can end up causing things like blood clots and thrumba embolism or blood clots are a really big cause of death for people
with cancer as well. So there's just a lot of ways that cancer dysregulates our body and then can end up leading to death, like in a lot of different ways.
Why are I know, I know that we're not going to talk about specific cancers, but why is there such very you know, looking at different organ system or like point of origin, organ of origin, Why is there such a difference tends to be such a difference in you know, metastasis and fatal you know, fatality and treatment receptibility. What is it being able to be treated? I can't think of the word.
It's hard, Aaron, because it's so many different things. I think that play into that. Some of it is our ability to screen for things, and so we are able to catch some cancers a lot earlier than we can catch other cancers, and therefore we can treat them more effectively with the same treatments that we would use for
another cancer. Pancreatic cancer is a really good example of that, like and ovarian cancer is another one where a lot of times these are completely asymptomatic until it's really bad, bad, until it's already spread at least regionally, if not widespread. And so that's part of it, whereas breast cancer, prostate cancer like things that we can screen for, we can potentially catch earlier. And some of it is just cancer
specific that I don't know the answer to. I'd have to dig on each specific cancer of like why pancreatic cancer is so so And some of it too, is that we research cancers that are more common, and there's more funding for cancers that are more common, which is logical, which means that cancers that are more rare are going
to have a lot less treatment options. They're going to be harder for us to detect, harder for us to even think about checking for, and then harder for us to treat because we don't have as many treatment options available for those kinds of cancers. And that's a really huge issue.
Right And then if they're if they're rarer, then it's harder to have clinical trials that then you know, show the performance of this treatment versus another.
So you're relying on a lot less data to guide your therapy to begin with. So there's there's so much that.
So many factors.
Yeah, but obviously cancer can and does end up affecting our entire body system. But I haven't even told you at all. How does this actually apply?
It happen?
How does a cell in our body just up and decide to go rogue? Is that really what happens? Why is tobacco, smoke and genetics? Like, how do all these virus environment genetics play a role. That is where we'll pick up next week here, Cliffanger, Cliffhangers, we love them, we do, we do. Gosh, I know it was a lot.
I feel like. I mean, yeah, we've we've covered a lot of grond already.
And I have so many more questions.
I know. I feel like we've also barely scratched the surface.
Yeah, that's true.
This is an iceberg of a top.
And if you want more below the surface, boy do we have very well?
Then we planned that, we did not plan that. We have a lot of sources. I have so many, And then I just wrote a few here to shout.
Out so long y'all, like please go to our website this podcast will kay you dot Com, click on the episode's tab and it.
Is such a long list it was really hard to stop. Yeah, and there are some really great sources. Okay, So for this episode, A few of the sources that I found the most helpful are The Emperor of All Maladies, A biography of cancer. It's classic, it's Pulser Prize winning. It is yes, by sid Arthur Mukerjee, published in twenty ten. Then there's another book called Terratologies, A Cultural Study of Cancer by Jackie Stacy, which I think this is twenty thirteen,
but I think it came out earlier than that. I'm not sure. That was a really interesting perspective on our perception of cancer today and how that's shifted. Then there's a series by had You from twenty eleven going all the way through like twenty sixteen or something like that, seven part series called A Note from History, Landmarks and History of Cancer one through seven. Hugely informative.
Okay, I love yeah.
And then also more about sort of the historical perception of cancer is a dread disease. Cancer in modern American culture by James Patterson nineteen eighty eight.
Not the same James Patterson that my dad reads.
I don't believe, so I'd have to double check on that.
I have a number of papers as well too. I also just want to shout out the National Cancer Institute has like a cancer classification. They have these like training modules that anyone can access.
There's a wealth of information there.
Yeah, it's really great. So I have a link to that. That paper that I mentioned that was like updating the definitions of cancer was by Brown at All from twenty twenty three, called Updating the Definition of Cancer. I thought that was just an interesting read. And then if you want more about the staging of cancer, there's a paper it's kind of old from two thousand and eight by Green and Sobin called the Staging of Cancer a retrospective and perspective appraisate.
Early twenty first century. I don't know.
And then there's so much more. Go to our website, check it out, you can see it at all. I'm done.
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And Tom and Leanna and so many Pete, Pete, Oh my gosh, I'm going to forget everyone's name. Oh dear.
Yes, thank you you make this happen. Also, I want to shout out my husband John for listening to me re all of these and go through all of these notes and talk incessantly about cancer for weeks on end and really every other topic. Yea.
I should also say thank you to Brat. I were listening to you. I mean him, It's like you can't do any fun things right now. I need to talk to you.
I want to talk to you about two hours about cancer. Your guys are good sports, very good sports. We appreciate your support. We also appreciate the support of listeners.
Good transition.
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Yes, it's the end.
It is of episode one. Of episode one, We've got three more coming to you, So wash your hands.
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