Speaker 1: Throughout this series, we'll be discussing many aspects of cancer
Speaker 1: diagnosis and treatment, and we will be sharing several personal
Speaker 1: stories related to cancer. Some listeners might find this content upsetting,
Speaker 1: Please listen with discretion.
Speaker 2: In the fall of twenty twenty four, I had just
Speaker 2: sent my oldest off to start his freshman year of college,
Speaker 2: and my youngest was starting high school. We had a
Speaker 2: very busy summer, and I was trying to settle in
Speaker 2: to our new normal. I'd started to gain weight earlier
Speaker 2: in the year, and even more recently, had started becoming
Speaker 2: very fatigued. When I talked to my godecologist about it
Speaker 2: at my checkup, we discussed that I was probably beginning perimenopause.
Speaker 2: Most of my symptoms seemed to line up. However, in
Speaker 2: late September, on a Sunday afternoon, I got a horrible
Speaker 2: stomach ache after eating lunch. The stomach ache persisted off
Speaker 2: and on for a few days, and I thought maybe
Speaker 2: I'd had food poisoning. It eventually got somewhat better, but
Speaker 2: I was still sore, and even made the comment to
Speaker 2: my coworkers that I felt like I had done a
Speaker 2: million crunches. I started to have cramping again one week later,
Speaker 2: again on a Sunday, but this time I was also
Speaker 2: having chills and nausea, so I went to an urgent
Speaker 2: care clinic where they did an X ray and said
Speaker 2: that I was constipated. However, they wanted me to follow
Speaker 2: up with my PCP the next morning. I was unable
Speaker 2: to see my PCP, but I did see an on
Speaker 2: call provider and she sent me for a CT scan. Thankfully,
Speaker 2: I was able to get it done that day. On
Speaker 2: my way home from the CT scan, the on call
Speaker 2: provider called me and told me to turn around and
Speaker 2: go to the emergency room as soon as possible. Her
Speaker 2: exact words were, your scan looks rough. I was septic
Speaker 2: and had emergency surgery the next day for a perforated bowl,
Speaker 2: and they also removed a suspicious part of my colon.
Speaker 2: It came back as stage two colon cancer. Genetic testing
Speaker 2: revealed that I had Lynch syndrome, which is a genetic
Speaker 2: condition that increases one's odds for gicholorectal, ovarian, uterine, and
Speaker 2: other types of cancers. I also tested positive for pot
Speaker 2: one tumor predisposition syndrome. Because of these markers, in the
Speaker 2: fact that my grandmother passed from ovarian cancer. I chose
Speaker 2: to have a complete hysterectomy, including ovaries. I also have
Speaker 2: to have yearly klonoscopies and egds, and other monitoring that
Speaker 2: needs to be done, including skin checks every six months,
Speaker 2: regular CT scans, and lab work. I feel very thankful
Speaker 2: to be ned or no evidence of disease at Jessha
Speaker 2: fifteen months, but I've made it my mission to inform
Speaker 2: and encourage my friends and family members to get their colonoscopy.
Speaker 2: I was forty five at the time of diagnosis and
Speaker 2: was able to start my screening that year, but I
Speaker 2: kept putting it off because I was too busy, and
Speaker 2: if I'm completely honest, I didn't think anything like this
Speaker 2: would happen to me. I considered myself relatively healthy. I
Speaker 2: ate right, I exercised, but my genetics had other ideas.
Speaker 3: Began in the fall of twenty twenty four with the
Speaker 3: weirdest diagnosis I could have never imagined for myself, and
Speaker 3: I've imagined tons of diagnoses. I'm a nurse and a
Speaker 3: burgo and an oldest child who grew up in the
Speaker 3: eighties and nineties who copes by catastrophizing, so trust me.
Speaker 3: I've diagnosed myself with plenty of things over the years,
Speaker 3: but not metasotic breast cancer. Of all the things that
Speaker 3: was not on my lifetime BINGO card. Among the many
Speaker 3: things that breast cancer has forced me to change it
Speaker 3: was that I have to be okay with vulnerability and frailty.
Speaker 3: I've never been comfortable with those things before. My body
Speaker 3: has really been through the ringer this past year, from
Speaker 3: surgery to chemo, to radiation now oral chemo.
Speaker 4: It has been.
Speaker 3: Poked, prodded, scanned, chopped up, stabbed, poisoned, and irradiated. I
Speaker 3: should have known what was in store for us when
Speaker 3: I was getting my implanted chemo port and they had
Speaker 3: to tape my breast to the side rail so that
Speaker 3: it wouldn't move and mess up the procedure.
Speaker 4: That was just the beginning.
Speaker 3: I have literally lost track of the number of people
Speaker 3: who have seen my breasts, the number of imaging procedures
Speaker 3: or scans I've had done. I never felt worse in
Speaker 3: my life than I have this past year, and I
Speaker 3: went to nursing school. There have been times I wanted
Speaker 3: to die just to let the cancer take me. My
Speaker 3: body betrayed me and not just by trying to kill me.
Speaker 3: It also made it so I had no control over
Speaker 3: things like my bowel or my bladder. I crapped in
Speaker 3: my pants when I thought it was just gas, or
Speaker 3: like that time when I peed on the sidewalk while
Speaker 3: walking my dogs.
Speaker 5: Super fun.
Speaker 3: Even now, my chemo brain is legit and I don't
Speaker 3: remember what it's like to not be nauseated. I've had
Speaker 3: to learn that I don't have to put a brave
Speaker 3: face on.
Speaker 4: I can be vulnerable.
Speaker 3: I can ask for help and I can share when
Speaker 3: my instinct really has always been to protect others from
Speaker 3: the ugliness that I've been facing. It doesn't diminish who
Speaker 3: I am as a caregiver. It really is okay to
Speaker 3: prioritize myself and my needs. That I can take time
Speaker 3: to listen to my body, and I can pause and
Speaker 3: I can rest. I have literally been fighting for my
Speaker 3: life and it's okay to take a day off. Thanks
Speaker 3: cancer for these epic life lessons. I'm better at advocating
Speaker 3: for myself now and listening to my body and its needs.
Speaker 3: It is okay to give myself grace. I do have
Speaker 3: to say, though I would give breast cancer zero stars.
Speaker 3: I do not recommend it.
Speaker 1: Thank you everyone who has shared your story with us,
Speaker 1: and also just a big thank you to everyone who
Speaker 1: wrote in to share your story. It is every time
Speaker 1: I just pinched myself and I'm so grateful that so
Speaker 1: many of you are willing to share these vulnerable experiences
Speaker 1: and because this really is like these first hand accounts
Speaker 1: are the backbone of this of this podcast. They bring
Speaker 1: so much that we couldn't that we could not, yeah.
Speaker 6: They absolutely do. This podcast would not be the same
Speaker 6: without your first hand accounts. So thank you so much,
Speaker 6: and we have a lot more that we'll be sharing
Speaker 6: with you throughout this episode and throughout the series as well.
Speaker 6: So thank you again to everyone who submitted your first
Speaker 6: hand account. We really wish that we could have included
Speaker 6: every single story that we had the privilege to hear,
Speaker 6: so thank you.
Speaker 5: It means a lot to us.
Speaker 7: It does. Hi.
Speaker 5: I'm Aaron Welsh and I'm Erin Onmann Update.
Speaker 7: And this is this podcast will kill you.
Speaker 6: Welcome to episode two of our series on cancer.
Speaker 5: It's a big one, it really is.
Speaker 1: If this is your first time tuning in to this series,
Speaker 1: go check out the first episode.
Speaker 7: We've got four total.
Speaker 1: Tom and for you, And each of these episodes covers
Speaker 1: a different aspect of cancer, and really are intent with
Speaker 1: this just just to lay the foundations of knowledge so
Speaker 1: that in the future we'll be able to then you'll
Speaker 1: be able to like, oh, yeah, I know what cancer
Speaker 1: is because in this episode on lung cancer, because I
Speaker 1: listened to the cancer.
Speaker 5: Series exactly exactly.
Speaker 8: Yeah.
Speaker 1: It gives us an opportunity to explore the big picture
Speaker 1: of what this all means. What does that mean? How
Speaker 1: are these episodes organized? Great question, I'd love to tell
Speaker 1: you if you didn't listen last week. Last week we
Speaker 1: really explored the concept of cancer from both like a
Speaker 1: biological perspective, well more clinical perspective, as well as like
Speaker 1: through history, how that has changed and our current conception
Speaker 1: of it. In this episode, we're going to be going
Speaker 1: over the evolutionary aspects of cancer, the cellular aspects of cancer,
Speaker 1: like why is cancer so prevalent?
Speaker 5: Right?
Speaker 1: Next episode treatment, last episode, Yeah.
Speaker 7: I mean that encompasses a lot.
Speaker 1: Yeah, And the last episode, the fourth and final, is
Speaker 1: all about screen prevention, kind of understanding the landscape of
Speaker 1: cancer today and where we might go from here.
Speaker 6: Exactly exactly, Yeah, And that's all quite a lot of
Speaker 6: ground to cover, but there's a lot that is going
Speaker 6: to be unexplored. And like you said, Arin, this is
Speaker 6: really the jumping off point. These are not the only
Speaker 6: cancer episodes that we are ever going to do. We
Speaker 6: have lots of plans to cover so many individual types
Speaker 6: of cancers, and we also have a massive list of sources.
Speaker 6: If anyone gets inspired and wants to learn more about
Speaker 6: cancer from a big picture perspective or individual cancers, my goodness,
Speaker 6: do we have sources for you.
Speaker 7: So many opportunities to do that. Yeah.
Speaker 1: Yeah, And as you'll hear, no two cancers or experiences
Speaker 1: with cancer are exactly alike. And so again we are
Speaker 1: just so grateful to the providers of our first hand
Speaker 1: accounts too. Really just showed us like a sample of
Speaker 1: what it means to have cancer, to be diagnosed with cancer,
Speaker 1: to be going through treatment, to lose someone to cancer,
Speaker 1: to be a caregiver, just so many diferent facets of
Speaker 1: this experience.
Speaker 5: That's so much of our lives.
Speaker 1: Yeah, that you know we're in these episodes, we're really
Speaker 1: talking about the biology of Like we're talking about from
Speaker 1: a biological and historical perspectives. We're not talking about these
Speaker 1: experiences and so that is where these first accounts have
Speaker 1: been so integral.
Speaker 6: So thank you again, thank you, thank you. They really
Speaker 6: do mean everything to us.
Speaker 7: Yeah, okay, one more piece of.
Speaker 5: Business, last piece of business.
Speaker 7: Quarantine ey time. We're still doing it.
Speaker 6: We're still doing it. If you didn't hear last week,
Speaker 6: we are no longer doing alcohol in our quarantine recipes.
Speaker 6: So you could consider them all plus e Brita's, but
Speaker 6: we're gonna call them Quarantini's.
Speaker 7: Just whatever strikes us.
Speaker 1: And this week we're drinking the Crab The Crabs Nafagatto.
Speaker 5: Espresso ice cream. Let's go get one after.
Speaker 1: This, Subscribe to our socials to Yeah, let's go get one.
Speaker 1: Subscribe to our socials to see how it's made. And
Speaker 1: check out our website where you can find all the
Speaker 1: other sorts of TPWKY things.
Speaker 6: This podcast would kill you dot com ye check it out,
Speaker 6: rate review, and subscribe. We're also on YouTube.
Speaker 7: Now for the real.
Speaker 5: Stuff, the real stuff.
Speaker 6: Okay, let us get in to the biology of cancer,
Speaker 6: shall we?
Speaker 7: We shall after this short break.
Speaker 8: On August twenty eighth, twenty five, I got a call
Speaker 8: from my dermatologist. He told me a biopsy on what
Speaker 8: I thought were hives had come back as malt lymphoma
Speaker 8: and asked me to come into his office so we
Speaker 8: could talk. What followed her months of emotional whiplash. At
Speaker 8: first I didn't understand the diagnosis. Then came long stretches
Speaker 8: of waiting, waiting to learn. My next steps were waiting
Speaker 8: for answers and finally get in information without a clear plan.
Speaker 8: Eventually a treatment plan came together, but the uncertainty leading
Speaker 8: up to it was one of the hardest parts. Malt
Speaker 8: lymphoma stands for mucosa associated lymphoid tissue lymphoma. It's a
Speaker 8: slow growing form of non Hodgkins lymphoma, and in my case,
Speaker 8: it appeared in my skin. I was told there are
Speaker 8: a few possible causes, including infections and genetics, but for me,
Speaker 8: the most likely explanation was simply bad luck. This type
Speaker 8: of lymphoma is considered rare and is more commonly found
Speaker 8: in men in their fifties and sixties. I was thirty one,
Speaker 8: active teaching and competing in country dance, and otherwise healthy,
Speaker 8: which made the diagnosis feel especially surreal. After consulting both
Speaker 8: my local oncologists and a noncologist at the Mayo Clinic.
Speaker 8: My husband and I decided on localized immunotherapy rather than
Speaker 8: surgery and radiation. I traveled to the Mayo Clinic in Scottsdale, Arizona,
Speaker 8: for treatment with RUTUXAMIV, which involved injecting the medication directly
Speaker 8: into the tumors. At the time, I had nine tumors
Speaker 8: across my arms. The process involved numbing injections followed the
Speaker 8: drug itself totally, about twenty to thirty injections per session.
Speaker 8: I have a high pain tolerance, but right after treatment
Speaker 8: my body started shaking and I felt extremely cold. It
Speaker 8: lasted about five minutes and then I was flying, but
Speaker 8: it was still unsettling. I remember looking at my husband
Speaker 8: and saying I wasn't sure I could do it again.
Speaker 8: I did. After three sessions, the tumors began to shrink.
Speaker 8: Six weeks after my last treatment, they have almost completely disappeared. Now.
Speaker 8: I continue regular monitoring. Any new bumps are considered a
Speaker 8: reoccurrence and something I may live with long term. While
Speaker 8: I'm grateful for an overall favorable prognosis, the experience permanently
Speaker 8: changed how I think about my health and my relationship
Speaker 8: with my body.
Speaker 9: When I was thirty two. In twenty sixteen, I was
Speaker 9: diagnosed with breast cancer. I found a lump in the
Speaker 9: shower once my local doctor, and within ten days I
Speaker 9: had been diagnosed. What followed was just a whirlwind. I
Speaker 9: had a right sided mystept to me and full node clearance.
Speaker 9: I had an immediate d AP reconstruction whether they took
Speaker 9: the fat from my stomach and made a new breast
Speaker 9: out of it. I had egg retrieval because we hadn't
Speaker 9: had children, and then I had six rounds of chemotherapy
Speaker 9: and radiation for three weeks. In twenty twenty five, nine
Speaker 9: years later, I'd had a sore hip and it was
Speaker 9: starting to affect my day to day life, so I
Speaker 9: went to the doctor. I saw the physio, who wasn't
Speaker 9: worried about it, went home, went on a trip where
Speaker 9: it felt like something had moved and I assumed I'd
Speaker 9: slipped a disc. So I came back went to the
Speaker 9: physio again, a female physio this time, and she referred
Speaker 9: me immediately. When I saw the physio at the hospital again,
Speaker 9: he wasn't too worried. I didn't have any massive red flags,
Speaker 9: but he sent me for an MRI just to make
Speaker 9: sure because I had a history of cancer. And at
Speaker 9: the end of March, I got a phone call to say, unfortunately,
Speaker 9: I had several deposits in my spine and in both
Speaker 9: hips and it looked like secondary breast cancer.
Speaker 4: I had to have a.
Speaker 9: Bone biopsy while I was awake, which I do not recommend,
Speaker 9: and I find out that, yeah, it definitely was cancer
Speaker 9: and I would have to be treated. At this point,
Speaker 9: I had no idea what that meant. I didn't know
Speaker 9: if it had spread. I didn't know if I had
Speaker 9: weeks or days or months left to live, and it
Speaker 9: just absolutely it was horrendous. That was nine months ago.
Speaker 9: I am medicated. I'm on a treatment called ribocyclip, which
Speaker 9: is a tablet, so I take it almost every day.
Speaker 9: It's really non invasive, and I'm now at the point
Speaker 9: where I only have to go into the hospital every
Speaker 9: two or three months. I hope that I continue to
Speaker 9: improve or stay stable, which is what my last couple
Speaker 9: of scams have showed. I know some people have been
Speaker 9: on this drug for eight ten years and I just
Speaker 9: still go in. So I really hope that I continue
Speaker 9: to live and thrive like I am doing now for
Speaker 9: a long time.
Speaker 8: To come.
Speaker 6: So I actually want to start this week's episode exactly
Speaker 6: where I started last week's episode, not where I ended it, okay,
Speaker 6: but where I started it, which is with the definition
Speaker 6: of cancer, Okay, which is the logical place to start.
Speaker 7: Yeah, yeah, It's like, yeah, sure.
Speaker 6: So I'll go back to that National Cancer Institute definitionat quote,
Speaker 6: cancer is a disease in which some of the body's
Speaker 6: cells row uncontrollably and spread to other parts of the body.
Speaker 6: So what does that really mean? If you've ever built
Speaker 6: a Lego Kit, you've built a Lego Kit at some
Speaker 6: point in your life.
Speaker 1: I've built Legos, but I don't know if I ever
Speaker 1: had a kit, Okay.
Speaker 6: So if you have ever built, if anyone listening and
Speaker 6: watching has built a Lego Kit, you could imagine that
Speaker 6: it comes with a set of instructions, Like if you
Speaker 6: want to build a rocket ship that really looks like
Speaker 6: a rocket ship, you're gonna need to follow the specific
Speaker 6: instructions that come in that Lego box.
Speaker 1: I mean, I've built many ikea pie the same kind
Speaker 1: of okay, very.
Speaker 5: Similar idea, just more pieces, et cetera.
Speaker 6: But in the box there are also a lot of
Speaker 6: different kinds of pieces of legos or Ikea bits, right,
Speaker 6: some of them all look the same. There's like fifteen
Speaker 6: different dowels, there's like twenty four different four by four
Speaker 6: squares or whatever. Yeah, and some of them look a
Speaker 6: little bit different from each other. And in order to
Speaker 6: build the thing you are trying to build, you have
Speaker 6: to follow those instructions really explicitly.
Speaker 1: I kind of I have to admit I love putting
Speaker 1: together Ikea furniture. You would love a Lego kit, then,
Speaker 1: I'm sure that I would.
Speaker 6: Our bodies are kind of the same. We have to
Speaker 6: function as one entire organism, a rocket ship, an Ikea
Speaker 6: piece of furniture.
Speaker 5: If you will.
Speaker 6: But we are made up of trillions of individual cells,
Speaker 6: and we started out as just one cell, which is
Speaker 6: a little bit different than Ikea furniture because our cell
Speaker 6: had to divide and divide a bunch of times. But
Speaker 6: this process of cell division is extremely tightly regulated. Yeah,
Speaker 6: because if every cell in our body just divided non stop,
Speaker 6: it would be madness.
Speaker 7: It would be a problem would be.
Speaker 5: We wouldn't be here in short.
Speaker 6: Yeah, So we have sets of instructions that are encoded
Speaker 6: into our DNA which have patterns, instructions that our cells
Speaker 6: are going to use to make the right types of
Speaker 6: tissue in the right types of places to grow and
Speaker 6: to replicate when it's appropriate to grow and replicate, and
Speaker 6: to not build a castle on top of your rocket
Speaker 6: ship out of all of your lego bricks.
Speaker 1: Right, it's like instructions on instructions on instructions. You will
Speaker 1: grow and replicate, but not only that, you're going to
Speaker 1: become this specific.
Speaker 7: Type of cell, specific type of specific type of organ
Speaker 7: in this specific little bit.
Speaker 6: And then you're going to forget how to do all
Speaker 6: those other things that you used to be able to do.
Speaker 5: We'll get there.
Speaker 6: So our cells determine when and how to divide based
Speaker 6: on a lot of different sets of instructions, and there
Speaker 6: is redundancy built into this process, and that is to
Speaker 6: protect against the inevitable mistakes that occur in the process
Speaker 6: of cell replication. So we have a lot of checkpoints
Speaker 6: in what is called our cells cycle and how our
Speaker 6: cells divide. Our cells rely on signals and communication with
Speaker 6: other cells. Like you mentioned, cells also differentiate, so they
Speaker 6: specialize into different types of cells in order to organize
Speaker 6: into tissues and organs, and then they only do that
Speaker 6: one certain thing your heart cell is just heart selling.
Speaker 6: It's not out here trying to be a skin cell anymore,
Speaker 6: even though they came from the same place. Right, Okay,
Speaker 6: So cancer cells kind of take all of the pieces
Speaker 6: out of a lego box, throw out the instruction manual,
Speaker 6: ignore any guidance on what these rules of building are
Speaker 6: supposed to be. So to really understand how this is happening,
Speaker 6: we can look through some of the rules of cell
Speaker 6: growth in detail and see how cancer cells are just
Speaker 6: breaking every single one of them. And and I know
Speaker 6: you're going to get it into this a little bit more, Aaron.
Speaker 6: They also leverage these rules in a way that benefits
Speaker 6: them and not us, So I'm I'm excited about that.
Speaker 5: So one of the rules that our.
Speaker 6: Cells typically follow is that they only grow and divide
Speaker 6: in the presence of what are called growth factors or
Speaker 6: growth signals, meaning that they're waiting for signals from cells
Speaker 6: and around them to determine if it is actually the
Speaker 6: right time to divide. Cancer cells either ignore these signals
Speaker 6: entirely or they just make their own. They just make
Speaker 6: their own growth signal, and then they're like, hey, we're
Speaker 6: telling you to grow, keep growing, So what we see
Speaker 6: and you talked about this in last week's episode. Arin
Speaker 6: In a lot of cancers are what are called oncogene mutations,
Speaker 6: and this means changes in certain genes that are involved
Speaker 6: in turning on growth, replication, and development signals all the time,
Speaker 6: which allows for this continuous cell division and growth of
Speaker 6: these masses of cells. So we see mutations in oncogenes
Speaker 6: in a lot of cancers. Almost all cancers have at
Speaker 6: least some oncogene mutations, and there are a few that
Speaker 6: are quite prevalent, like a few big ones that are
Speaker 6: prevalent in nearly all cancers. So you might have heard
Speaker 6: of some of these when you're looking at cancer things.
Speaker 6: Some of these are like RAS or ris yep, and
Speaker 6: there's a bunch of different versions of RAS, and these
Speaker 6: are things that basically, when they are switched on, they
Speaker 6: just allow for cells to continue to grow uncontrollably, and
Speaker 6: they're switched on in a lot of cancers.
Speaker 7: Gas Pedal to the floor.
Speaker 5: Gas pedal to the floor.
Speaker 6: Another mechanism that you also talked about a little bit
Speaker 6: last week's episode is that all of our cells typically
Speaker 6: have the ability to turn off cell division if they
Speaker 6: need to turn it off. Entirely, and they're able to
Speaker 6: recognize if our cells and the DNA within our cells
Speaker 6: gets damaged, so that they can stop that process of
Speaker 6: cell division if there's damaged cells or damaged DNA, and
Speaker 6: not replicate that damaged DNA. One of the ways that
Speaker 6: we do this in our cells typically is through a
Speaker 6: process called apoptosis, which is programmed cell death, and it
Speaker 6: basically is that our cells are recognizing damage and they're
Speaker 6: saying this cell, you need to dye, this cell you
Speaker 6: need to die and done exactly, and then our immune
Speaker 6: system comes in and they do the thing.
Speaker 4: They do the job.
Speaker 6: Cancer cells, you can guess, turn these mechanisms off.
Speaker 7: Yep.
Speaker 5: And a lot of the.
Speaker 6: Genes involved in this process we call tumor suppressor genes,
Speaker 6: and in cancer, these mechanisms are turned off.
Speaker 2: Yep.
Speaker 6: That's the get take out. The break of the cop
Speaker 6: is broken. It's completely gone. And there are a lot
Speaker 6: of different kinds of tumor suppressor genes. But I'm going
Speaker 6: to give everyone a concrete example because then I think
Speaker 6: we'll be able to connect it back. Yeah it's brakka,
Speaker 6: oh okay, okay. Gave me a face like it was
Speaker 6: going to be something different. I don't know, it will
Speaker 6: be something different the face that you're making. Yeah, but
Speaker 6: Braca wanted Bracket, who I think most of us has
Speaker 6: probably heard of. These are the genetic mutations that are
Speaker 6: associated with a significantly increased risk of breast cancer, ovarian cancer,
Speaker 6: but also melanoma's, pancreatic cancer, lots offerent types of cancers,
Speaker 6: and these are tumor suppressor genes. So if somebody is
Speaker 6: born with a certain version of these genes, the certain
Speaker 6: copy of brak of one or brack of two, then
Speaker 6: they are not making a protein. And in this case,
Speaker 6: the protein is supposed to help identify and repare broken DNA.
Speaker 6: So if you can't do this, if you can't identify
Speaker 6: and repair broken DNA, then your cells have a tendency
Speaker 6: to accumulate more mutations and that leads to this increased
Speaker 6: risk of cancer. But there is another classic tumor suppressor
Speaker 6: that I feel obligated to talk about because it is
Speaker 6: its function is affected in almost every case of cancer,
Speaker 6: and that is TP fifty three.
Speaker 7: That's what I thought you were going to talk about.
Speaker 5: That's what I figured.
Speaker 7: What what proportion of cancers?
Speaker 6: Well, okay, fifty percent of cancers have a mutation in
Speaker 6: this specific gene TP fifty three. Yes, but almost all cancers,
Speaker 6: over ninety percent have some kind of mouth function of
Speaker 6: the function of this P fifty three protein. So this
Speaker 6: TP fifty three gene encodes for a bunch of different
Speaker 6: versions of this specific protein that does so many different
Speaker 6: things in our cell cycle. It activates DNA repair proteins,
Speaker 6: It halts the cell cycle if there is damage to DNA,
Speaker 6: it initiates apoptosis. It's involved in a process called sinescence,
Speaker 6: which is very important in cancer biology and is like
Speaker 6: when our cells age to a point where our body
Speaker 6: decides stop replicating forever.
Speaker 7: You're too hard to keep an eye on.
Speaker 6: Exactly, You're unreliable at this point. I'm taking away the keys,
Speaker 6: you know. And we see mutations in this particular gene,
Speaker 6: like I said, in half of all human cancers, and
Speaker 6: disruption of the function. So even if the gene is
Speaker 6: still making the protein somewhere something else, the protein can't
Speaker 6: do its job anymore. So this particular gene is really
Speaker 6: important in cancer formation.
Speaker 7: It's a big deal.
Speaker 6: It's a really big deal. There's a condition where people
Speaker 6: could be born with a non functional copy of this
Speaker 6: gene and that results in a condition called leaf from
Speaker 6: any syndrome.
Speaker 7: Next week's book book Club episode.
Speaker 6: Oh amazing, Yes, oh so definitely listen to that one.
Speaker 6: And that you are prone to a wide variety of
Speaker 6: cancers with leaf from any syndrome, and usually quite early
Speaker 6: in life compared to when we typically see cancers. But
Speaker 6: there's more. There's more that cancer cells do. Cancer cells
Speaker 6: also they start to upregulate, so like encourage this process
Speaker 6: that keeps them alive indefinitely. So most of our other
Speaker 6: cells can only divide a certain number of times, and
Speaker 6: then at a certain point they start making mistakes that
Speaker 6: are completely deleterious to the cell, so then they just
Speaker 6: can't do it. Cancer cells have enzymes that they make
Speaker 6: to keep our DNA viable to continue replicating forever. Override override, override, switch,
Speaker 6: override switch. We also see that cancer cells alter how
Speaker 6: they do metabolism.
Speaker 7: Yeah, they do.
Speaker 5: They alter how they.
Speaker 6: Do mytabolism in ways that allow them to survive better.
Speaker 6: For example, they can survive better in low oxygen environments.
Speaker 6: They can adapt to whatever nutrients are available in the environment.
Speaker 6: And speaking of oxygen, because oxygen is really important for
Speaker 6: all of our cells to be able to grow. And
Speaker 6: the way that our cells get oxygen in our bodies
Speaker 6: is through our blood stream, of course, and to get
Speaker 6: blood you need blood vessels because that's where our blood
Speaker 6: happens to be contained. So cancerous tumors up regulate the
Speaker 6: process of angiogenesis, which is the formation of blood vessels,
Speaker 6: so they make their own blood vessels in order to
Speaker 6: feed themselves. We also see changes like modifications of the
Speaker 6: genome that aren't just mutations, other ways that they change
Speaker 6: the genome without having to have an actual DNA mutation
Speaker 6: in there. We see that they can also we set
Speaker 6: how cells have to differentiate and become like only a
Speaker 6: heart cell. Cancer cells can undo that differentiation to make
Speaker 6: cells look more like stem cells, which divide indefinitely and
Speaker 6: can do any sorts of function, etc.
Speaker 7: Yeah, we can do whatever, take whatever form right exactly.
Speaker 6: So that's like on the tiniest little micro level, all
Speaker 6: of our cells are doing this really weird and wacky stuff.
Speaker 6: On the slightly more macro level, looking a little bit
Speaker 6: bigger at like the cancers and their environment, if we will.
Speaker 7: The ecology of a tumor.
Speaker 6: Ecology of a tumor, they have really big impacts on
Speaker 6: things like our inflammatory system. And what's so interesting is
Speaker 6: that cancers activate our inflammatory system, they activate our immune
Speaker 6: system and pathways across basically all cancers, and yet they
Speaker 6: also are incredibly good at avoiding our immune system's destructive processes.
Speaker 6: So they are using the parts that benefit them as
Speaker 6: inflammation brings oxygen, it brings blood, it brings other cells
Speaker 6: and things like that, but then they are still evading
Speaker 6: the destructive process our immune system that would normally get
Speaker 6: rid of them. And of course, like I mentioned last week,
Speaker 6: one of the biggest things that cancerous tumors do, or
Speaker 6: that cancer cells do in general, is that they are traveling. Yes,
Speaker 6: they are traveling widely throughout our body. Individual cells, clumps
Speaker 6: of cells are breaking off, and they are traveling throughout
Speaker 6: our body, which can then cause additional disease in distant areas.
Speaker 6: So cancer cells do a lot, and a lot of
Speaker 6: these changes are due to mutations in our DNA that
Speaker 6: are allowing for some of this evasion of typical checkpoints
Speaker 6: like the continued replication and things like that. But we
Speaker 6: also can see a lot of these types of mutations
Speaker 6: in people that will never develop cancer, and in a
Speaker 6: lot of our so called normal cells, like the same
Speaker 6: mutations can be present, but there's no cancer there. And
Speaker 6: that is why cancer is not just a genetic disease.
Speaker 6: It's a disease of what we call g by E
Speaker 6: or genetic and environmental interactions. So the mutations that we
Speaker 6: know are associated with cancer are a necessary but not
Speaker 6: sufficient part of cancer biology.
Speaker 1: A cancer of cell doesn't turn cancers simply because it
Speaker 1: has one mutation exactly exactly.
Speaker 6: These mutations can arise spontaneously. We might be born with
Speaker 6: some of them, but they also could arise from exposures
Speaker 6: to things that are actually mutagens, and that might be
Speaker 6: like tobacco smoke, which has so many different carcinogens in
Speaker 6: it that do in fact cause damage to our DNA
Speaker 6: and can result in some of these dileterious changes, or
Speaker 6: like a virus like you talked about last week, inserting
Speaker 6: some of these oncogenes into our DNA. But there also
Speaker 6: has to be something that stimulates these type of mutations
Speaker 6: to actually persist and take over.
Speaker 5: So we now know, and we don't fully understand this all, Aaron, but.
Speaker 6: That some of especially the environmental exposures, might contribute in
Speaker 6: more ways than just affecting our DNA, right, So, like, yes,
Speaker 6: tobacco smoke is going to damage your DNA and inhibit
Speaker 6: DNA repair and increase your mutation burden. But a lot
Speaker 6: of exposures also are going to potentially just create an
Speaker 6: environment in our cells and in our tissue, whether that's
Speaker 6: increase in inflammation, whether that's whatever it is that we
Speaker 6: don't fully understand this like tumor micro environment effect, but
Speaker 6: we know that it's an essential part of this cancer
Speaker 6: formation process. And that's where we think that a lot
Speaker 6: of these environmental exposures that we don't fully understand the
Speaker 6: direct links how those might be playing.
Speaker 7: A role mechanistically.
Speaker 1: It's not just about the genetic changes, it's also about
Speaker 1: these other things that allow for that soul to evade
Speaker 1: immune detection or to get nutrients or whatever that expect
Speaker 1: these different factories exactly.
Speaker 6: And I feel like what this really underscores is how
Speaker 6: much of a kind of perfect storm of events has
Speaker 6: to happen for cancers to be able to develop. And
Speaker 6: it also helps us know why aging is such an
Speaker 6: important risk factor, because the more that your cells divide,
Speaker 6: the more likely any of these mutations might take place.
Speaker 6: But you really do have to have the right sets
Speaker 6: of mutations in the right cells, in the right environment,
Speaker 6: with the right supporting cell cast at the right time
Speaker 6: for these cancer cells to be able to take hold
Speaker 6: and eventually take over.
Speaker 1: It's a perfect storm, but it's storming all the time.
Speaker 6: It's storming all the time, right, And while all cancers
Speaker 6: break all of these different rules that I went over,
Speaker 6: every single one does it in slightly different ways.
Speaker 1: That pathway is different, different progression is different, that mutations
Speaker 1: might be different, that you know, nutrient whatever.
Speaker 6: Everything is exactly every individual exposure that you've had, your
Speaker 6: particular DNA and how it's interacting with those exposures. And
Speaker 6: that is why it makes it really hard to generalize
Speaker 6: our treatments for cancer. Even if we're like, but this
Speaker 6: is the same receptor or this is the same mutation,
Speaker 6: this is the same protein. Why isn't this treatment working
Speaker 6: exactly the same?
Speaker 8: Yep?
Speaker 6: Right, So really, cancer is I'm really wanting you to
Speaker 6: start talking, Aaron, because cancer is kind of our cells
Speaker 6: forgetting how to function as a multicellular organism.
Speaker 7: Yeah, it's our.
Speaker 6: Cells all of a sudden, but not all of a sudden,
Speaker 6: because it's a long process, but starting to live as
Speaker 6: parasites as these like unicellular organisms that no longer abide
Speaker 6: by all of the r that makes them good neighbors
Speaker 6: to all of the other cells around them.
Speaker 7: But they also do cooperate within a tour.
Speaker 6: Ooh, I can't wait for you to tell me all
Speaker 6: about that, Aaron. And they do, and they cooperate with
Speaker 6: that particular environment, and they make it very conducive for
Speaker 6: themselves and themselves only, and they're leveraging our body systems
Speaker 6: in order to do this. So erin, I'm hoping that
Speaker 6: you can shed some light on the evolution of cancers
Speaker 6: and why it is that we are so susceptible to these.
Speaker 1: It's so funny that you've said shed some light, because
Speaker 1: I literally say something just like that.
Speaker 5: I can't wait.
Speaker 10: Hey. My name is Kendra and I am thirty three.
Speaker 10: I was diagnosed with stage three c ovarian cancer in
Speaker 10: twenty twenty four. My diagnosis came as a surprise as
Speaker 10: I didn't have any signs or symptoms to think that
Speaker 10: I needed to be seen for anything. I was just
Speaker 10: going in to get my ID replaced and needed an ultrasound,
Speaker 10: and then they found the ovarian cancer. Sadly, ovarian cancer
Speaker 10: doesn't have a lot of noticeable signs or symptoms, and
Speaker 10: so it was a fluke that it was found. After
Speaker 10: being sent to gynecology oncology to figure out a treatment plan,
Speaker 10: I was sent off for some genetic testing where I
Speaker 10: found I was also BRACKO. When positive with the brackagene,
Speaker 10: I have an increased risk of cancer such as breast
Speaker 10: ovarian cancer, as well as pancreatic cancer and some other cancers.
Speaker 10: Along with getting myself genetically tested, my doctor also sent
Speaker 10: my cancer off to be genetically tested, where they were
Speaker 10: able to find a few different treatment plans that would
Speaker 10: be helpful that were specifically targeted towards my type of cancer.
Speaker 10: This has been an overwhelming and scary process, and I
Speaker 10: have learned so much about the medical research that has
Speaker 10: been done and the advancements that we've made looking at
Speaker 10: genetics and how it impacts people's risks for cancer.
Speaker 4: Hi.
Speaker 5: My name is Michelle.
Speaker 11: I'm forty two years old and I live on Long Island,
Speaker 11: New York. My husband Ed was diagnosed with glioblastoma, which
Speaker 11: is the most aggressive form of brain cancer, in July
Speaker 11: of twenty twenty four and passed away in October of
Speaker 11: twenty twenty.
Speaker 4: Five at forty four years old.
Speaker 11: We're the parents of a teenage son, and Ed was
Speaker 11: a talented radio producer, so speaking about his experience on
Speaker 11: a podcast is actually something that really connects to who he.
Speaker 4: Was in his professional life.
Speaker 11: Ed had a sinus infection and then for two weeks
Speaker 11: following had intermittent pressure headaches.
Speaker 4: Urgent care said it's probably a.
Speaker 11: Lingering sinus infection, and he went to his primary care doctor,
Speaker 11: who said, let's get an MRI just in case, because
Speaker 11: why take the chance, so scheduled MRI. A couple of
Speaker 11: days before the MRI, he came to me and said,
Speaker 11: this isn't getting any better. And I said, why don't
Speaker 11: you just go to the er just for peace of mind.
Speaker 11: I actually googled whether or not a headache was a
Speaker 11: good reason to go to the er. And he drove
Speaker 11: himself and said, don't cancel our dinner plans. And three
Speaker 11: hours later he called me and said you need to
Speaker 11: get here now. They found something on the cat scan,
Speaker 11: and thankfully we only lived five minutes from the hospital.
Speaker 11: It was an incredibly traumatic fourteen and a half months.
Speaker 11: And when I say this, was the shock of our lives.
Speaker 11: It's a tremendous understatement. There's so much I could discuss
Speaker 11: about our experience, but one thing that stands out is
Speaker 11: that glio blastoma's not common at our age, so it
Speaker 11: was so isolating going through this and him seeing that
Speaker 11: he was the youngest person in the waiting room every
Speaker 11: single time. When he was looking for support groups for himself,
Speaker 11: it was mostly people who were twenty to third years older.
Speaker 11: When I was looking for caregiver support groups, it was
Speaker 11: mostly children taking care of parents or retired couples, and
Speaker 11: we were like, where are all the people who are
Speaker 11: working full time, who had to put their careers on hold,
Speaker 11: who have to caregive full time while also making sure
Speaker 11: their school age children's routines are intact and have extracurricular
Speaker 11: activities to take their kids to. The worst was when
Speaker 11: people would see us and say, you're too young to
Speaker 11: be dealing with this, and I'm trying to navigate that
Speaker 11: as a widow right now. Apparently the universe didn't get
Speaker 11: the memo that we're too young to be dealing with this.
Speaker 1: We learned last week that cancer has been our unwelcome
Speaker 1: companion for all of human history, ancient medical descriptions of
Speaker 1: tumors and fossilized hominid remains with probable cancerous growth. They
Speaker 1: defy the labeling of cancer as solely a disease of modernity.
Speaker 1: And yet, despite millennia of human evolution, despite the recent
Speaker 1: decades of cancer research, despite the thousands who have devoted
Speaker 1: their lives to finding a cure, despite the hundreds of
Speaker 1: thousands of millions who have also participated in finding this cure,
Speaker 1: we still struggle to effectively treat, or prevent or even
Speaker 1: define this disease.
Speaker 5: Yeah.
Speaker 1: Why to answer that, we have to rethink cancer from
Speaker 1: an entirely different perspective. Rather than seeing cancer as this
Speaker 1: single entity that can only be defeated through a full
Speaker 1: scale attack, we can use evolution to grasp the nuance
Speaker 1: and complexity that drives cancer development, which hopefully will also
Speaker 1: steer us away from that military language of wars and
Speaker 1: battles implying winners and losers and us versus them. Yes,
Speaker 1: as you just explained Aaron, cancer cells are a part
Speaker 1: of us. Why would cancer grow so out of control
Speaker 1: if that results in the death of its host and
Speaker 1: thus the cancer itself. Wow, why is cancer so common?
Speaker 7: In humans.
Speaker 1: Shouldn't we have evolved to resist it?
Speaker 7: It just doesn't make sense, does it?
Speaker 2: Though?
Speaker 1: Then again, paraphrasing theodosious Dubjanski, nothing in cancer biology?
Speaker 7: He says, nothing in.
Speaker 1: Biology makes sense except in the light of evolution. I
Speaker 1: challenge you to find a paper on cancer evolution that
Speaker 1: does not reference to Jansky's. Yeah, so let's shine that
Speaker 1: evolutionary light on cancer. This is a story told in
Speaker 1: four parts. The first deals with seeking to understand the
Speaker 1: evolution drivers of cancer cells. Why do they proliferate? Why
Speaker 1: do they spread? The second involves the defenses that we
Speaker 1: have evolved to prevent or control CANCEROSK growth. The third
Speaker 1: scans for patterns across the animal kingdom in cancer resistance
Speaker 1: and susceptibility, And the fourth and final part asks how
Speaker 1: can we apply this evolutionary knowledge to design better strategies
Speaker 1: for cancer treatment?
Speaker 7: Today?
Speaker 6: Ah, Aaron, I can't tell you. I've been waiting for
Speaker 6: this episode for so long.
Speaker 1: This episode really was like a shift for me in
Speaker 1: being like, oh, this is not some I know you
Speaker 1: called cancer parasite, but it's not like it is just
Speaker 1: a product of evolution.
Speaker 7: That's it.
Speaker 5: I love it.
Speaker 1: It doesn't want to survive. It just does because it
Speaker 1: happens to have evolved those certain traits anyway.
Speaker 7: Okay, so Part one.
Speaker 1: When it comes to the deep evolutionary roots of cancer,
Speaker 1: our hominid fossils reveal the merest tip of the iceberg.
Speaker 8: Fact.
Speaker 1: Even older specimens with suspected cancers on the order of
Speaker 1: tens of millions of years, like in the case of
Speaker 1: duck billed dinosaur fossils, which showed cancer to hundreds of
Speaker 1: millions of years, we're still in iceberg tip territory. The
Speaker 1: true origins of cancer extend back to the first multicellular life.
Speaker 1: When life on Earth began roughly four billion years ago,
Speaker 1: single celled organisms ruled the roost, and they did so
Speaker 1: for the next two billion years. During that unfathomably long
Speaker 1: period in which individual cells battled individual cells, cancer did
Speaker 1: not exist.
Speaker 5: That is so, I mean like it.
Speaker 1: It could not exist because, by its very definition, uncontrolled
Speaker 1: growth of abnormal cells cancer requires other normal cells to
Speaker 1: stand out. In contrast, uncontrolled growth is only uncontrolled in
Speaker 1: comparison to what is considered controlled. So it was only
Speaker 1: two billion years ago when cells began to coalesce and
Speaker 1: coordinate to form multicellular organisms that cancer was possible. Wow, multicellularity,
Speaker 1: it's a great strategy.
Speaker 7: It's a great way to go pretty well.
Speaker 1: I mean, imagine, instead of doing everything yourself, you divvy
Speaker 1: up tasks like cleanup or resource gathering, and you can
Speaker 1: accomplish much more than you could on your own. It's
Speaker 1: true what they say, there's strength in numbers. Multicellularity depends
Speaker 1: on cooperation on a massive scale. We like to think
Speaker 1: of ourselves as individuals, as individual thinkers, you know, with our.
Speaker 7: Own lives so unique.
Speaker 1: But really what we are is a massive population of
Speaker 1: cells with different jobs and locations and genetic identities. And
Speaker 1: not all are human cells. We've got lots of non.
Speaker 5: Humans humans, possibly more than our human selves.
Speaker 4: Possibly.
Speaker 1: This cooperation is really quite astounding if you think about it.
Speaker 1: In her book, The Cheating Cell Researcher Athena Ectopus presents
Speaker 1: what she calls the multicellularity playbook. I like this in
Speaker 1: contrast to like think about this, in contrast to the
Speaker 1: hallmarks the cancer hallmarks hallmarks of cancer Number one, don't
Speaker 1: divide out of control. Number two, self destruct if you're
Speaker 1: a threat.
Speaker 7: Yeah.
Speaker 1: Number three, Share and transport resources. Number four, do your job,
Speaker 1: division of labor.
Speaker 8: Yeah.
Speaker 1: Number five, take care of the environment. Oh, if only
Speaker 1: we could all basically just I know the rules of
Speaker 1: multi cellularity.
Speaker 7: I mean, listen just too much.
Speaker 1: We could even go into there, but basically it comes
Speaker 1: down to do your job, be respectful, and everything's going
Speaker 1: to be hunky doors.
Speaker 5: We're all going to be chill and living together.
Speaker 7: It's great.
Speaker 6: Clean your dishes out of the thing, put them in
Speaker 6: the dishwasher.
Speaker 4: Just is it that hard.
Speaker 7: Hick up after yourself?
Speaker 1: Yeah, And of course we know that things don't always
Speaker 1: go that way.
Speaker 5: They don't.
Speaker 7: They rarely always go that way.
Speaker 1: Cooperation is vulnerable to exploitation by cheaters, and when sells
Speaker 1: don't follow the multicellularity playbook, cancer can result cancer cells.
Speaker 1: They're not consciously cheating and intending to get a leg
Speaker 1: up on all these cooperative suckers. It's simply evolution. So ourselves,
Speaker 1: as you said, are constantly replicating to grow, to develop,
Speaker 1: to replace damage cells. In this process involves copying the
Speaker 1: DNA within our cells. With all that copying, a few
Speaker 1: errors are bound to slip in there. Most of the time,
Speaker 1: we've got these self defense mechanisms or these little checkpoints.
Speaker 1: Those mistakes are or to make you check up on things.
Speaker 1: Maybe the mistakes are harmless, maybe they're repaired, or maybe
Speaker 1: the mistakes are too big and the cell is earmarked
Speaker 1: for destruction. Yeah, but on occasion, those mutations will slide
Speaker 1: under the radar. And let's say that one of those
Speaker 1: mutations tells the cell to proliferate rapidly with no off switch,
Speaker 1: and another maybe helps it evade the defense mechanisms whose
Speaker 1: job it is to catch these out of control cells.
Speaker 1: I've got this renegade cell with the gas pedal to
Speaker 1: the floor and the breakout of commission. In no time,
Speaker 1: that cell becomes two, then four, then eight, then sixteen,
Speaker 1: and so on.
Speaker 5: That's how cell division works, yep.
Speaker 1: And all of these daughter cells are then inheriting those
Speaker 1: same mutations. These cells, they're not playing by the rules
Speaker 1: of multicellularity playbook, and in an evolutionary sense, they're doing great.
Speaker 1: There's no conscious thought to like, I want to evade,
Speaker 1: I want to take these resources. Oh that's a new resource.
Speaker 1: Let me take that. It's the cells that happen to
Speaker 1: evolve the mutations that allow them to take advantage of
Speaker 1: this environment.
Speaker 6: They are just growing because they can't grow, grow yep, yep,
Speaker 6: that's it. And spread and spread, yeah, because they can.
Speaker 1: It's because the mutations evolve. And so ultimately, if this
Speaker 1: proliferation continues unchecked, it will result in the death of
Speaker 1: the entire organism, which includes the cancer cells themselves.
Speaker 5: Which is a bad thing.
Speaker 8: Right.
Speaker 1: So we've got these cancer cell out competing normal cells.
Speaker 1: But if that ultimately kills the organism, how can that
Speaker 1: be evolution? Like, isn't that just a dead end? It
Speaker 1: is for that individual cancer which will go extinct when
Speaker 1: its host dies. Extinction is not a new concept, and
Speaker 1: this is also asterisk for if you're a transmissible cancer story.
Speaker 1: But like dinosaurs have gone extinct, humans have killed off
Speaker 1: many different.
Speaker 7: Species many in the past.
Speaker 6: We have made go extinct, you know how many thousands
Speaker 6: of years. Yes, it's part of the process of evolution.
Speaker 1: Part of the process of evolution, right, And I think
Speaker 1: it also is important to remember that evolution works on
Speaker 1: different time scales. Yes, So to quote from Ectipus's the
Speaker 1: cheating cell quote. From the perspective of our bodies, cancer
Speaker 1: is a threat to our survival and well being. From
Speaker 1: the perspective of the cell, cancer cells are only doing
Speaker 1: what every other living thing on this planet does, evolving
Speaker 1: in response to the ecological conditions they are in, sometimes
Speaker 1: in ways that are detrimental to the system of which
Speaker 1: they are apart end quote.
Speaker 5: It's just it's just evolution.
Speaker 7: It's just evolution.
Speaker 1: Yeah, And I'm not We're not saying that to minimize it, no,
Speaker 1: but just to explain, like, this is not some you know,
Speaker 1: parasite that's coming in and wanting to take advantage of
Speaker 1: this and doing this and that.
Speaker 6: But I mean, even parasites are just evolution, Yeah, exactly, right,
Speaker 6: Like that's the thing. They're not like, they don't have agency,
Speaker 6: they're not trying to kill us. It's just that they are.
Speaker 6: Those particular cells are surviving. They're surviving, that is all
Speaker 6: they are doing.
Speaker 1: And the ones that do survive are the ones that
Speaker 1: have the right characters, right tools, the right characters, and
Speaker 1: that particular environment that.
Speaker 6: It is that environment at that time, yeah, yeah, and
Speaker 6: evolution is working on that population of cells.
Speaker 8: Right.
Speaker 1: So because cancer is not a one time event, no,
Speaker 1: those renegade cells will continue to evolve as long as
Speaker 1: there is genetic variation, which is why we see diversity
Speaker 1: within tumors. Nor is cancer just cancer cells. The tumor
Speaker 1: micro and environment both influences and is influenced by the
Speaker 1: cells that comprise it, both cancerous and non cancerous. There's
Speaker 1: collagen to hold the tumor together, blood vessels that deliver resources,
Speaker 1: even immune cells that have been reprogrammed by the cancer
Speaker 1: cells to tell other cells don't worry about it, just
Speaker 1: move along. Some cancer cells might be more clonal, so
Speaker 1: like genetically identical than others, but genetic and tissue diversity
Speaker 1: is a feature of cancer, which is what makes it
Speaker 1: so difficult to treat. Cancer is not a homogeneous tissue.
Speaker 1: It is instead an evolving, dynamic mass of genetically diverse cells.
Speaker 1: Within that mass, some cells might be super susceptible to
Speaker 1: a type of treatment, while others are more inherently resistant.
Speaker 1: If that treatment is administered, you would expect the resistance
Speaker 1: cells to increase in number, because those are the ones
Speaker 1: left over. This is why resistance emerges so often after
Speaker 1: cancer treatment, and why oncologists combine different treatments and again,
Speaker 1: these cancer cells, they're not replicating uncontrollably or evolving resistance
Speaker 1: because they're evil or want.
Speaker 5: To, so they're trying to kill you.
Speaker 7: They have simply inherited the instructions to do so. Part two.
Speaker 1: Defense against cancer that chaotic growth, the seizing of resources,
Speaker 1: the resistance to destruction. These are not new weapons created
Speaker 1: by cancer cells.
Speaker 7: These are all qualities.
Speaker 1: That are normal cooperative cells already possess. If these features
Speaker 1: can do such harm when expressing a cancer cell, why
Speaker 1: do they evolve at all? Because proliferation and differentiation are
Speaker 1: foundational to our growth and development. When we're growing, is
Speaker 1: embryos and fetuses than infants, healing a wound, fighting an infection,
Speaker 1: going through puberty, reproducing, replacing the lining of our intestinal tractor, skin, proliferation, differentiation, movement,
Speaker 1: and resource utilization. These are what makes us multicellular organisms.
Speaker 1: If our cells exert too strong of a control over
Speaker 1: these processes, our development or our fertility might be negatively
Speaker 1: impacted as a result. So think back to our second
Speaker 1: episode in our pregnancy series when we talk about the
Speaker 1: placenta and there's this like kind of push pull where
Speaker 1: it's like, this is a really challenging experience for your
Speaker 1: body to be like, Okay, this thing is growing inside
Speaker 1: me and it's kind of like me, but it's not.
Speaker 7: Quite well, not quite like me, and so how much
Speaker 7: do I give and take?
Speaker 1: And it's a little bit of a balance there, and
Speaker 1: it's sometimes hard to strike. And so there's this thought that, like,
Speaker 1: cancer is one of the costs of higher fertility because
Speaker 1: there's more tolerance for things that are like you, but
Speaker 1: I don't like you.
Speaker 5: Yeah, just a little off. Oh that's super interesting.
Speaker 7: Right, it's a tightrope.
Speaker 1: So if these processes are allowed to continue unchecked, though,
Speaker 1: cancer might be the outcome. So it's either you are
Speaker 1: hold you know, too tight of a control over them
Speaker 1: and then you'd stay nation right and under development, or
Speaker 1: not enough control.
Speaker 5: And then you end up with cancer. Yeah. Oh that's
Speaker 5: so interesting.
Speaker 1: Yeah, this is the crux of cancer, the constant tightrope
Speaker 1: walk that we do as organisms to balance chaotic growth
Speaker 1: with stagnation. As Actipus puts it, quote, this leads to
Speaker 1: the counterintuitive conclusion that the optimal level of cancer risk
Speaker 1: for an organism is not zero.
Speaker 8: Right.
Speaker 1: Yeah, that is to me, that's like the bottom line
Speaker 1: of everything. Yeah, that cancer is the consequence of multicellular
Speaker 1: life for growth and division, reproduction.
Speaker 5: Right, it's all of the things that we already do.
Speaker 5: It's just doing too much.
Speaker 1: Yeah, the near ubiquity of cancer across multicellular organisms demonstrates
Speaker 1: that cancer is an unavoidable consequence of complex multicellular life,
Speaker 1: one that can shorten life span and impact fertility to
Speaker 1: a considerable Just because we have a multicellularity playbook doesn't
Speaker 1: mean everyone follows these rules, and so we've evolved different
Speaker 1: strategies to catch and eliminate those cheaters. The first is intrinsic.
Speaker 1: So our cells you'd kind of talked about this. Our
Speaker 1: cells contain within them these intrinsic mechanisms to monitor for
Speaker 1: any funny business, big mistakes in DNA transcription, wonky proteins,
Speaker 1: or something else that signals that the cell might not
Speaker 1: be following the multi cellularity playbook. If something abnormal is detected,
Speaker 1: that information is processed and then a quote unquote decision
Speaker 1: is made. There's no conscious thought here, just using it
Speaker 1: as a shortcut. Can the cell be repaired? Should we
Speaker 1: shut down replication until the error is fixed? Should the
Speaker 1: cells self destruct? This is where something like TP fifty
Speaker 1: three comes in. Our famous tumor suppressor gene also known
Speaker 1: as the Guardian of the genome, which I really.
Speaker 5: Love, I know, And so that sounds so noble, I know.
Speaker 1: So TP fifty three takes in all this information and
Speaker 1: it initiates the appropriate response. And that's just one example
Speaker 1: of our intrinsic defenses against cancer. We've got many other strategies,
Speaker 1: like preventing or repairing DNA copying mistakes in the first place.
Speaker 1: And then in addition to these intrinsic mechanisms, we've also
Speaker 1: got the neighborhood watch. This is pretty much what it
Speaker 1: sounds like. Cells keep an eye on their close neighbors
Speaker 1: for any sign that something suspicious is going on, looking
Speaker 1: little binoculars through the window.
Speaker 5: Like what times it's just like that, what's that app
Speaker 5: everyone's using next Door next Door?
Speaker 7: Yeah, it's just it's just like that is.
Speaker 1: And so for the most part, our cells are quite
Speaker 1: sensitive to self destruction. You just give them a funny
Speaker 1: look and they're like, okay, fine, I guess I'll just
Speaker 1: self destruct. They're committed to cooperation, and so often it's
Speaker 1: it's not so much like that the neighbor cells have
Speaker 1: to be like self destruct. It's more just like if
Speaker 1: the neighbor cells like, you're not you're not right, Like
Speaker 1: they want constant positive reinforcement and so if their neighbor
Speaker 1: cells like, I'm just it's it's not doing it for me.
Speaker 1: It's not me, it's you, Right, then they're like, okay,
Speaker 1: I guess we'll just self destruct.
Speaker 7: Yeah, and.
Speaker 1: The neighbor cells will eventually be like, you need to
Speaker 1: self destruct if it's like if they're like, come on,
Speaker 1: take a hint.
Speaker 7: So okay.
Speaker 1: So our cells have got these internal monitoring systems, their
Speaker 1: neighbors are keeping a watch on them, and then there's
Speaker 1: this more global line of defense the immune system. Right,
Speaker 1: our immune system is constantly scrutinizing cells for any signs
Speaker 1: of cheating, like excessive proliferation, consuming too many resources, and
Speaker 1: avoiding instructions to self destruct. One of the ways our
Speaker 1: immune systems do this is to detect tumor antigens, which
Speaker 1: are these proteins expressed on the surface of certain cancer cells.
Speaker 1: The immune system reads as a signal that the cells
Speaker 1: behaving inappropriately, and if they detect one of these antigens,
Speaker 1: they can tell other cells search and destroy anything expressing
Speaker 1: this antigen. It's basically like what they do to viruses,
Speaker 1: exactly destroy.
Speaker 7: Yeah.
Speaker 1: So these three primary means of cancer suppression are continuously
Speaker 1: monitoring for any signs of trouble. And when you think
Speaker 1: about the thirty trillly and or so cells in our body,
Speaker 1: I have a citation for that.
Speaker 5: No, yeah, I saw thirty to forty Yeah, yeah, yeah, bananas.
Speaker 1: And I was like, it is also brilliant to write
Speaker 1: this paper. You will be cited so frequently.
Speaker 7: Because everyone's going to be like, how many cells manybody else?
Speaker 5: Very billion?
Speaker 7: We find it. We find it on Google scholar.
Speaker 1: Yeah, but when you think about all these cells, it's
Speaker 1: pretty astonishing how good of a job our body does
Speaker 1: most of the time when it comes to monitoring for
Speaker 1: any signs of disruption.
Speaker 6: Seriously, and like, if you really know how many times
Speaker 6: we make mistakes in DNA replication, it is fascinating that
Speaker 6: it doesn't that cancers and other deleterious mutations don't arise
Speaker 6: more frequently, right, I.
Speaker 1: Mean, and this is a reflection of millions of years
Speaker 1: of evolution billions. When we look at an age distribution
Speaker 1: of cancer diagnoses, most happened later in life, and comparatively
Speaker 1: in comparatively few happen in childhood, despite childhood being a
Speaker 1: time of rapid cell proliferation and differentiation. As we grow
Speaker 1: mature there is stronger selection for those cancer suppression mechanisms
Speaker 1: at an early age because the cost of cancer through
Speaker 1: an evolutionary lens, like the fitness cost, is greater. That
Speaker 1: selection relaxes a bit as we get older. And to
Speaker 1: be clear, I'm not suggesting that it's worse than when
Speaker 1: cancer happens in a child compared to an adult. Cancer
Speaker 1: is awful no matter when it happens. I'm simply saying
Speaker 1: that these cancer defense mechanisms were more likely to be
Speaker 1: passed down because they conferred a benefit for survival and reproduction,
Speaker 1: especially earlier in life, to our whole organism, to all
Speaker 1: our whole organism. Yes, and remember again it's a tightrope.
Speaker 1: These defense mechanisms don't always function perfectly because there's a
Speaker 1: trade off between chaos and stagnation. If having a bigger
Speaker 1: body means better survival or reproductive viability, then you don't
Speaker 1: want to restrict proliferation or differentiation too early. Same with
Speaker 1: wound healing, same with tissue repair, making new blood cells,
Speaker 1: and so on. How do different species balance this trade off?
Speaker 8: Like?
Speaker 7: What patterns exist? Part three?
Speaker 1: Okay, cancer across the animal kingdom? Okay, there are cancerous
Speaker 1: growths and plants and.
Speaker 7: Yes, and fungi. I'm not going to talk about it.
Speaker 5: They're so interesting and cool looking now they're.
Speaker 1: Very cool, but it's that's too big for this is
Speaker 1: already Yeah, I know, I know, but it is true.
Speaker 5: It's all multicellular organisms and plants.
Speaker 1: Yeah, yeah, almost all. I've read some stuff about sponges
Speaker 1: that I did, I took out, but anyway, bunges, so
Speaker 1: they just sort of like pinch it off and they're like.
Speaker 5: They're like, you're disease anymore by Yeah.
Speaker 1: Yeah, that's cool, kind of like what our guts do
Speaker 1: a little bit. It's it's very cool.
Speaker 4: Yeah.
Speaker 1: So, knowing what we know about cancers, what are some
Speaker 1: patterns we think we might find. Okay, broadly speaking, cancer
Speaker 1: happens when a cell acquires mutations that a let it
Speaker 1: throw out that multicellularity playbook and b escape detection and
Speaker 1: destruction by cancer suppression mechanisms. All it takes for cancer
Speaker 1: to develop is one cell going rogue and the right
Speaker 1: environ anything else, but you know what I mean, you
Speaker 1: still need the initial do you need the potential?
Speaker 8: Yes?
Speaker 1: Yeah, so you might expect that the more cells there are,
Speaker 1: the greater.
Speaker 7: The risk of cancer.
Speaker 5: Do we see that, Aaron?
Speaker 1: Okay, So if this were the case, what we might
Speaker 1: expect to find is that elephants, blue whales, rhinos, and
Speaker 1: other large bodied species should have higher rates of cancer
Speaker 1: than small ones like mice, bats, small birds, and longer
Speaker 1: lived species like giant tortoises and humans whose cells have
Speaker 1: a lot longer to accumulate cancerous mutations, should also have
Speaker 1: a higher risk of cancer compared to those with relatively
Speaker 1: short or comparatively short lifespans like shrews and hedgehogs. That's
Speaker 1: not what we find interesting. In fact, there seems to
Speaker 1: be no correlation at all between longevity, body size, and
Speaker 1: cancer across species.
Speaker 5: Huh.
Speaker 7: So this surprising finding has a name.
Speaker 1: It's called pedos paradox, Pedo's paradox, Pedo's paradox. So elephants,
Speaker 1: despite having one hundred times the amount of cells that
Speaker 1: humans do, do not have one hundred times the risk
Speaker 1: of cancer. In fact, elephants are less likely to develop
Speaker 1: cancer compared to humans.
Speaker 5: Interesting.
Speaker 7: On the other end of the scale, mice are more
Speaker 7: likely to develop cancer than humans are really really, no.
Speaker 5: One talks about that, I know, not just the mice
Speaker 5: we grow in labs.
Speaker 7: I presume I don't.
Speaker 1: I mean, so this is where don't get me started
Speaker 1: on the data viability. There are multiple papers that discuss
Speaker 1: about like the limitations of Pedo's paradox and the observations
Speaker 1: that have been used to formulate anyway. Okay, so however,
Speaker 1: though within a species the pattern is there, the expected
Speaker 1: pattern that we see. So bigger dogs are more likely
Speaker 1: to develop cancer than smaller.
Speaker 7: Dogs, Taller humans are.
Speaker 1: More likely to develop cancer compared to shorter humans, and
Speaker 1: the same goes for age again within species.
Speaker 5: Okay, yeah, how interesting.
Speaker 7: Yeah, so why might this pattern across species?
Speaker 8: Have?
Speaker 6: They got to have something else going on? It's got
Speaker 6: I mean, there's other protective mechanisms.
Speaker 7: Many different possible answers.
Speaker 1: Right, Larger species might have lower mutation rates overall, they
Speaker 1: might have more tumor suppressor genes. This actually has been
Speaker 1: found in elephants who have twenty copies of TP fifty three.
Speaker 1: You heard to humans two copies.
Speaker 5: I've learned that one. Yeah, I knew that one, obviously
Speaker 5: forgot it, but I learned that one.
Speaker 7: It's we blew my mind, yeah, in my mind.
Speaker 1: Uh, there, maybe the there's a species immune systems could
Speaker 1: be more tuned into precancerous or cancerous cells. Their cells
Speaker 1: might be more sensitive to a self destruct signal. It's
Speaker 1: even been suggested that larger animals develop larger tumors that
Speaker 1: then them cells are destroyed by cancer cells, where it's
Speaker 1: like tumor infighting. Interesting kind of thing, Like there's something
Speaker 1: about like, yeah.
Speaker 6: Just then the way that it interacts with their immune
Speaker 6: system it's going to be different that yeah.
Speaker 5: Interesting.
Speaker 1: So in short, yeah, there are a number of different
Speaker 1: hypotheses as to why larger bodied and longer lived species
Speaker 1: have less cancer than we'd expect. Pedo's paradox might also
Speaker 1: reveal different trade offs in life history strategies. So take
Speaker 1: a mouse, for example, which matures to reproductive age pretty quickly.
Speaker 1: To take advantage of that quick development time, you might
Speaker 1: want to step on the proliferation gas, so to speak,
Speaker 1: even if that comes with a higher risk of cancer.
Speaker 1: And this is actually what we have found when it
Speaker 1: comes to chicken farming. Chickens that are selected for early
Speaker 1: egg laying and higher production tend to have higher rates
Speaker 1: of ovarian cancer.
Speaker 5: Oh interesting, because they're like, make more.
Speaker 1: Eggs, make egg proliferate, proliferate proliferate, and elephants which mature
Speaker 1: later on might invest more in cellular watchfulness earlier in life,
Speaker 1: interesting just to make sure that they survive to reproductive age.
Speaker 1: Of course, so Pedo's paradox has been revisited repeatedly since
Speaker 1: it was first introduced in the nineteen seventies, and researchers
Speaker 1: have argued that there is no paradox if you analyze
Speaker 1: the data this way, or if the paradox grows stronger
Speaker 1: if you analyze it that way, or depending on where
Speaker 1: you're getting your data on all this stuff, but there
Speaker 1: seems to be no getting around the observation that from
Speaker 1: the existing data that we have cancer risk is lower
Speaker 1: than we would expect in larger bodied and longer lived species.
Speaker 1: Beyond Pedo's paradox, there are a few other patterns that
Speaker 1: researchers have observed. Birds and reptiles tend to have less
Speaker 1: cancer than placental mammals species in Carnivora, mammals that eat
Speaker 1: flesh tend to have higher cancer risk. This might be
Speaker 1: because of biomagnification, so like carcinogenic compounds have accumulated at
Speaker 1: the top of the food chain. A low fiber and
Speaker 1: high fat diet and potentially cancer causing pathogens.
Speaker 7: Found in raw meat.
Speaker 5: Interesting, Okay, Yeah.
Speaker 1: Deer that grow large antlers every year rapid cell proliferation
Speaker 1: tend to have higher rates of cancer. And there's some
Speaker 1: other stuff about like sexually selected traits like that that
Speaker 1: involve making big things, and species that have undergone a
Speaker 1: genetic bottleneck. The Santa Catalina Island foxes tend to have
Speaker 1: higher rates of cancer. Prevalence for them is greater than
Speaker 1: fifty percent really, so that suggests that genetic diversity, especially
Speaker 1: when it comes to immune diversity, is really important when
Speaker 1: it comes to being protective against cancer.
Speaker 6: There's so many levels that I'm loving this eran, but
Speaker 6: also just I feel like I have seen on the
Speaker 6: internet people being like, but cancer only happens in humans. No, no, no,
Speaker 6: And like just the diversity already that you've said.
Speaker 5: Oh, there's yeah, I know, I know, you know the internet.
Speaker 7: I know I do know the internet.
Speaker 1: If I'm familiar, you've heard of it, I've heard of it.
Speaker 7: We're quite close.
Speaker 1: There's also other environmental or developmental drivers that could play
Speaker 1: a role in cancer risk across species. You know, if
Speaker 1: you're a species' if that's exposed a lot to UV radiation,
Speaker 1: Maybe you're more likely to get cancer, Maybe you're more
Speaker 1: likely to evolve defense against that kind yeah, yeah, right,
Speaker 1: The rate of healing might be positively associated with cancer risks.
Speaker 7: So if you're a fast healer, you might have higher
Speaker 7: risk of.
Speaker 6: Cancer because again, the immune system mechanisms and the inflammatory
Speaker 6: process and the wound healing process uses a lot of
Speaker 6: those same features that cancers exploit.
Speaker 5: The kind of thing, yep, yep.
Speaker 1: And this is by no means an exhaustive list of
Speaker 1: the patterns that we see in cancer risk across the
Speaker 1: animal kingdom. Nor does it fully explain the lifetime cancer
Speaker 1: risk in humans of forty percent, because even though we
Speaker 1: have these mechanisms that lower our risk of cancer, they
Speaker 1: don't take it to zero. And we talked about why
Speaker 1: that's probably not possible. Right, The ideal risk for cancer
Speaker 1: is not zero from an evolutionary perspective when it comes
Speaker 1: to proliferation and differentiation, But forty percent might also reflect
Speaker 1: an evolutionary mismatch. Cancer is a consequence of multicellularity, yes,
Speaker 1: but the environment that we live in now is different
Speaker 1: than the one in which we evolved. Exact things like cigarettes,
Speaker 1: processed meets, our sedentary lifestyle, our increased longevity.
Speaker 7: All of these things lead.
Speaker 1: To a higher risk of cancer alcohol, and correspondingly, they
Speaker 1: lead to a need for a better approach to treatment.
Speaker 7: Part four.
Speaker 1: Okay, how can we apply what we know about cancer
Speaker 1: evolution to design treatments that outmaneuver rather than outright attack cancer.
Speaker 1: Even if you had never heard of treatment resistant cancer before,
Speaker 1: the concept of resistance would probably be familiar to it.
Speaker 1: Antibiotic resistant bacteria like MRSA or pesticide resistant insects show
Speaker 1: us that resistance is a useful and expected trait that
Speaker 1: emerges in a biological target after a powerful onslaught.
Speaker 5: In the context of evolution, Aaron.
Speaker 1: In the context of evolution, it's the same old story, right.
Speaker 1: You target a susceptible population with some type of treatment.
Speaker 1: Maybe that's penicillin, maybe that's DDT, maybe that's chemotherapy. Maybe
Speaker 1: that wipes them all out, or maybe a few invulnerable
Speaker 1: individuals remain. Those few multiply into many, and now you've
Speaker 1: got a fully resistant population against which you are powerless.
Speaker 1: This can happen in an individual receiving cancer treatment. Over time,
Speaker 1: the cancer may stop responding to those therapies, and this
Speaker 1: is a major issue in cancer that contributes to significant
Speaker 1: mortality every year, and we struggle, we continue to struggle
Speaker 1: to contend with it. So, faced with this substantial challenge,
Speaker 1: some cancer researchers have taken inspiration from other fields outside
Speaker 1: of cancer ancer, like agriculture, to devise ways to minimize
Speaker 1: the emergence of resistance in the first place. One approach,
Speaker 1: called adaptive therapy is modeled after integrated pest management.
Speaker 5: Integrated pest management.
Speaker 1: Yeah, yeah, which is an agriculture roba, I know.
Speaker 8: So.
Speaker 1: Integrated pest management is an agricultural technique that assumes resistance
Speaker 1: will eventually and so you delay the inevitable as much
Speaker 1: as you can. You utilize small doses rather than massive blast,
Speaker 1: with a goal of long term control rather than eradication.
Speaker 1: Adaptive therapy, which is the cancer version of this, is
Speaker 1: intended to keep cancer cells sensitive to the drugs, and
Speaker 1: it has the added benefit of doing less damage to
Speaker 1: the surrounding tissue. The key is monitoring and adjusting the
Speaker 1: dose or timing according to how the tumor is responding.
Speaker 1: So if the tumor grows, you might want to increase
Speaker 1: the dose. If the tumor shrinks, lower the dose or
Speaker 1: just stop giving some meds. If it stays the same,
Speaker 1: either you know, keep the dose the same or back
Speaker 1: off a little.
Speaker 7: It works.
Speaker 1: I mean, it's basically like a thermostat. You're just like, okay,
Speaker 1: how do we get to seventy two.
Speaker 6: You're not trying to get rid of anything, You're just
Speaker 6: trying to not let it get any bigger.
Speaker 1: Yeah, And sometimes maybe getting rid of something means getting
Speaker 1: your immune system to step in. Sometimes it means just
Speaker 1: like slowing things down right. And so by employing this approach,
Speaker 1: you're selecting for slower dividing cells, and you're relaxing that
Speaker 1: pressure to develop resistance and for resistance to be the
Speaker 1: key defining trait of this tumbor. No resistance mechanisms can
Speaker 1: be really costly to maintain, so if there's no need
Speaker 1: for them, those resistance cells might be out competed by
Speaker 1: sensitive ones. I came across a great analogy explaining this
Speaker 1: that I really I really like. So think about like
Speaker 1: a big bulky umbrella. Okay, this is our resistance mechanism. Okay,
Speaker 1: it's heavy, it's annoying.
Speaker 7: You have to lug it around everywhere.
Speaker 5: With you always forget it, always forget it.
Speaker 7: If it's raining all the time, i e.
Speaker 1: Big doses of chemotherapy, the inconvenience is totally worth it
Speaker 1: and you're probably not going to want to leave it somewhere.
Speaker 1: But if it's mostly sunny or just occasional drizzles, you're like,
Speaker 1: you're going to forget it a cafe and not think
Speaker 1: about it.
Speaker 5: You're just wear my raincoat.
Speaker 1: Right, can be fine, and so resistance can also, like
Speaker 1: you can, cells can also evolve to no longer be
Speaker 1: resistant if there's not that pressure to maintained resistance. So
Speaker 1: the beauty of adaptive therapy is that it's both generalizable
Speaker 1: and personal. Right, you can use this with any existing Theoretically,
Speaker 1: it can use us with any existing drug or treatment,
Speaker 1: and you're constantly tweaking the dose or timing based on
Speaker 1: how that individual tumor is responding.
Speaker 6: And it could be with any drug. Right, any drug
Speaker 6: that initially shows a benefit, you could do it with.
Speaker 7: You could do that.
Speaker 1: Yeah, So sounds great in theory. Is there any clinical evidence.
Speaker 7: To back it up?
Speaker 1: Tell me there is the first clinical trial testing adaptive
Speaker 1: therapy was conducted ten years ago. In twenty sixteen on
Speaker 1: people with metastatic prostate cancer whose cancer was no longer
Speaker 1: responding to hormone therapy. Those who received adaptive therapy had
Speaker 1: a median time to progression of twenty seven months compared
Speaker 1: to the sixteen and a half months time to progression
Speaker 1: with standard treatment. So that's an extra eleven months, ten months,
Speaker 1: eleven months, that's huge, huge, huge, So it slowed tumor
Speaker 1: growth in that way, it actually slow the progression of
Speaker 1: the disease. And with adaptive therapy, the chemotherapy dose was
Speaker 1: cut in half, suggesting that this approach could lead to
Speaker 1: fewer side effects and lower medical costs, which is a
Speaker 1: concern in this country. Since that first trial, a handful
Speaker 1: of others have begun on prostate and ovarian cancer, and
Speaker 1: several of which are still underway or I think in
Speaker 1: the works right now. But even though its early days,
Speaker 1: adaptive therapy seems like a really promising area of cancer research,
Speaker 1: and it's important to point out that this is not
Speaker 1: for every case of cancer. Some cancers are going to
Speaker 1: respond better to some therapies than others, and researchers have
Speaker 1: devised different criteria for determining when a cancer might be
Speaker 1: treated with an aggressive versus an adaptive approach, like when
Speaker 1: what is going to result in the outcome that we
Speaker 1: most want or like the ideal outcome, but especially when
Speaker 1: it comes to cases where a cure seems unlikely, adaptive
Speaker 1: therapy may be able to control or delay progression. Another
Speaker 1: tactic is decoy drugs. Have you come across this?
Speaker 8: No?
Speaker 7: Okay? Love this?
Speaker 1: So these are used for treatment resistant cancers, and I
Speaker 1: also don't like I haven't read extensively on the existing literature,
Speaker 1: but so like this is more of like the as
Speaker 1: it was explained in a theoretical.
Speaker 7: Basis, but resistant cells.
Speaker 1: So they've there are some resistance that that involves evolving
Speaker 1: pumps to pump out the chemotherapy before it can do
Speaker 1: any harm. Because chemotherapy, I know, we'll talk about it
Speaker 1: next week, but basically its goal is to kill.
Speaker 7: Se it's just killing, it's killing cells, and so it's
Speaker 7: like this is a toxic thing. Pump that out. Yeah,
Speaker 7: And so the idea with.
Speaker 1: These, with these pumps is that they pump out the
Speaker 1: chemotherapy drugs before it can do any harm. And that's
Speaker 1: how resistance works in those cells. These decoy drugs can
Speaker 1: take advantage of that. They don't do anything to the cancer,
Speaker 1: but they appear like dangerous chemicals. So those cells continuously
Speaker 1: pump them out. They're like, oh my gosh, it's coming.
Speaker 1: It's gonna kill me. It's gonna kill me. I'm gonna
Speaker 1: pump it out, pump it out. This is constant work.
Speaker 1: Exhaust the cells, It deeply its resources, and it makes
Speaker 1: them expend too much energy to replicate. So the goal
Speaker 1: with these therapies.
Speaker 6: Is not to actually do anything to the cells except
Speaker 6: just keep them busy.
Speaker 7: Keep them busy so interesting, exhaust them.
Speaker 1: So it's not it's it's not to eradicate, it's not
Speaker 1: to destroy. It's just to anticipate cancer's next move or
Speaker 1: even guide that next move. Interesting, So, for instance, there's
Speaker 1: one thought is that cancer cells become more likely to
Speaker 1: invade to a new area if their tumor environment becomes
Speaker 1: hostile or resource depleted, like what would happen with aggressive
Speaker 1: chemo and radiation and radiation.
Speaker 7: And so there's this.
Speaker 1: Idea that like maybe maintaining that tumor, and again this
Speaker 1: is very dependent upon the individual the cancer, but maintaining
Speaker 1: that tumor at that size, maybe that would prevent the
Speaker 1: cancer from spreading. So instead of shrinking the tumor, instead
Speaker 1: of attacking the tumor, we just keep it.
Speaker 5: Content how it is. Yeah, the cells just don't let
Speaker 5: it do its invasion thing.
Speaker 7: Yeah. Yeah.
Speaker 1: Or what if we directed evolutions so that benign cells
Speaker 1: quote unquote we're encouraged to grow over malignant ones.
Speaker 7: How do you kind of do that?
Speaker 1: You can kind of lead it down and like into
Speaker 1: an alley and then trap it cancer.
Speaker 7: I mean, this is sort of the idea.
Speaker 1: Yeah, we could also support our own bodies ability to
Speaker 1: detect or eliminate cancer aus cells, which I'm assuming you're
Speaker 1: going to talk about next week. It is extremely encouraging
Speaker 1: to see the incorporation of evolutionary principles into cancer treatment,
Speaker 1: and it's something that is long overdue. So there was
Speaker 1: an analysis published in twenty eleven where authors estimated that
Speaker 1: one percent of all papers about cancer recurrence or resistance
Speaker 1: that were published since the nineteen eighties mentioned anything about evolution.
Speaker 1: One percent talked about evolution. Ongoing research on cancer evolution,
Speaker 1: tumor ecology, and adaptive therapy.
Speaker 7: It holds the power to transform the way that we
Speaker 7: under stand and treat cancer.
Speaker 1: And I'm really excited to see where this research will
Speaker 1: take us, But only looking back on the journey that
Speaker 1: brought us here can we appreciate how far we've already come.
Speaker 1: Oh this is so true, Aaron, So stay tuned for
Speaker 1: next week when we talk about cancer treatment.
Speaker 5: Another great cliffhanger.
Speaker 7: Thank you.
Speaker 5: What a journey erin I I just it.
Speaker 1: Really helped me to think of cancer cells as just
Speaker 1: successful in an evolutionary context, using the tools that they
Speaker 1: already had in our normal.
Speaker 5: Cells, which I honestly still like.
Speaker 6: That is why they seem like a population of bacteria
Speaker 6: to me.
Speaker 5: But like, but they're not, I know, there us. So
Speaker 5: they have all of our traits and like all of this.
Speaker 1: Bacterial cells have, you know, certain toxins or certain whatever.
Speaker 5: They have other things that they and we don't.
Speaker 1: And the cancer cells are working with the toolkit that
Speaker 1: every single one of our cells already has, And that
Speaker 1: true blows my mind.
Speaker 5: Yeah, yeah, it's true. That's true. They're just acting like
Speaker 5: they're not a part of.
Speaker 1: Us, right, yeah, they're like, well, I mean I'm just
Speaker 1: I have this this new trait.
Speaker 5: So yeah, sorry, sorry, little bit, it's better for me. Yeah, yeah,
Speaker 5: it is so interesting.
Speaker 6: But well, next week, we'll have a lot more for you.
Speaker 6: But if you want to read more, oh boy.
Speaker 7: Oh yeah we do.
Speaker 5: We sure have a lot of sorts. I always go first,
Speaker 5: you do, yeah, I think's gesture to you.
Speaker 7: Uh okay.
Speaker 1: So the Cheating Cell by Athenactipus, I thought it was
Speaker 1: absolutely fascinating.
Speaker 5: Love it great, great.
Speaker 6: Dive into almost lash and then I was like, oh,
Speaker 6: I think Aaron is reading, so I'm.
Speaker 4: Gonna not.
Speaker 7: Because we're friends on good Reads.
Speaker 1: Then there's a paper by Colin and Mally Peter's Paradox
Speaker 1: Evolutions Prescription for Cancer Prevention from twenty eleven. And then
Speaker 1: if you want to read sort of a nice little
Speaker 1: overview of adaptive therapy by Saying at All from twenty
Speaker 1: twenty three in Critical Reviews and Oncology Hematology.
Speaker 4: Love it.
Speaker 6: I have a good number of papers for this episode.
Speaker 6: I think a couple to shout out. There's like three
Speaker 6: papers going from two thousand to twenty twenty two by
Speaker 6: Hannahn and Weinberg, and one is just by handah hand
Speaker 6: that are like called the Hallmarks of Cancer. So those
Speaker 6: are kind of like the classic.
Speaker 7: I have a few of those.
Speaker 5: Yeah. And then there's a.
Speaker 6: Couple that are like pushing back against the hallmarks of cancer, which,
Speaker 6: like I don't think change things all that much.
Speaker 5: But I have a few of those as well too.
Speaker 7: Catch title them Yeah they got they got me.
Speaker 6: But but some of them are good and they really
Speaker 6: just talk more about the micro environment. So one of
Speaker 6: them that I particularly liked is over a Century of
Speaker 6: Cancer Research Inconvenient Truths and Promising Leads by Snishine and
Speaker 6: Sodo from twenty twenty. But again, there's a bunch more.
Speaker 6: I don't even know which other oness to shout out.
Speaker 4: There's so others.
Speaker 7: There're so many lots.
Speaker 6: More on the mechanisms of carcinogenesis from environmental things. If
Speaker 6: you want that, you can find them all on our website. Yes,
Speaker 6: this podcast will kill you dot com.
Speaker 7: It's truly a massive list. You happy reading, Happy reading.
Speaker 5: Every one. You're welcome.
Speaker 6: Everyone writing their term papers like, thank you and seriously.
Speaker 5: Seriously, we did it for you. You're welcome.
Speaker 7: Yes, thank you.
Speaker 1: Thank you also to the providers of our first hand accounts.
Speaker 7: Again. Yeah, what what can we say that hasn't already
Speaker 7: been said? Thank you from the bottom of our heart.
Speaker 6: We can't thank you enough. Is the truth of it.
Speaker 6: So thank you, thank you, thank you, thank you.
Speaker 1: I'm honest say thank you again to Bloodmobile in addition
Speaker 1: to John and Brett for.
Speaker 6: Yes, those are our husbands, we thank them before and
Speaker 6: Bloodmobile my brother brother.
Speaker 5: For the music.
Speaker 7: For the music.
Speaker 5: Yeah, we really appreciate you, Yes we do. Thank you
Speaker 5: to everyone here at the Exactly Right Studios. Thank thank you.
Speaker 6: To Tom and Leanna and Pete. Thank you to Jessica
Speaker 6: and Sabrina and Boomer. We're gonna thank everyone today. I
Speaker 6: remembered names.
Speaker 1: Oh my god, I've got this so many thank yous
Speaker 1: to go around. Thank you to our listeners. Thank you
Speaker 1: to our patrons. You all make this possible.
Speaker 5: I hope you guys enjoyed this episode. Yeah I did.
Speaker 7: Yeah, it's really tell us what you think.
Speaker 6: It's interesting. We've got a lot more coming, so make
Speaker 6: sure you subscribed.
Speaker 7: And until next time, wash your hand.
Speaker 5: You felt the animals
Speaker 3: U