Timestamps:

[00:01] Intro: Paul Roach, MD; Peter Schlagel, MD; Michael Riordan, Man of the People

[01:30] Short definitions of What is Cancer?

[04:30] Framing:  What is life?

[04:37] Shout out to Lex Fridman's awesome Podcast- Thanks, Lex

[06:40] What is a Cell?

[07:15] Long definition of or exploration of “What is Cancer?”

[19:00] Mutations of cell signaling, growth, and, differentiation

[30:00] Detecting Cancer

[43:00] Tumor markers

[46:00] Hereditary mutations

[53:30] Genetic Testing & Counseling

[1:02:00] Genetic Signatures

[1:04:00] Smoking, Age, Obesity, Heredity

[1:10:00] The Basics

[1:12:00] Targeted Therapy

[1:16:50] Where cancer cells go wrong

[1:23:02] Benign versus Cancerous

[1:29:27] Summary and Closing

Links:

https://www.nasa.gov/vision/universe/starsgalaxies/life's_working_definition.html

https://www.quantamagazine.org/what-is-life-its-vast-diversity-defies-easy-definition-20210309/

https://youtu.be/yyBosLx7bbM

https://youtu.be/NXU_M4030nE

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cell

https://www.cancer.gov/about-cancer/understanding/what-is-cancer

References:

https://www.goodreads.com/book/show/18442853-the-molecular-basis-of-cancer?from_search=true&from_srp=true&qid=Sw4zWg3ZSp&rank=1

https://www.goodreads.com/en/book/show/61048190-devita-hellman-rosenberg-s-cancer

Key Takeaways:

“Life” as we know and accept it is the product of an intricately organized set of self-sustaining bio-chemical processes working harmoniously, with memory and the ability to carry-on over time and over new generations (Paul’s best crack at the question of “what is life?”).

Biological life is comprised of individual cells, which are extremely tiny and have three main parts:  cell membrane wall around it; cytoplasm filling it up; and a nucleus as the main office or command center of the cell containing the DNA / genetic code, which determines the structure and the behavior of the cells and the tissues. 

In life, that DNA/genetic code acquires (or sometimes is born with) “defects” or “mutations” which alter the shape, function, and behavior of the cell; some types of mutations [particularly those responsible for the processes/jobs of cell signaling, cell growth, and cellular differentiation] result in derangements and loss of proper cellular function —which brings its own set of problems— and also, aggressive behaviors of local invasion and distal metastasis —which, untreated, can produce organ system failure and death.

Normal cellular machinery is so complicated that there are 10,000 ways (my made up number) in which it can break down, which in short accounts for the great variability of ways in which cancer can evolve and manifest.

These multiple pathways make it impossible to treat with a “one size fits all” approach, but these days we’re learning how to identify and target with a variety of clever treatments many of those various pathways, and thereby individualize treatment to that specific, unique tumor.

Advice: Cancer happens, but to minimize your risk of cancer / advanced cancer, take the best care of your own health with diet, exercise, moderation of things like tobacco / food / alcohol that you can, and keep a regular relationship with your physician for periodic check ups, screening exams, and the sharing of your family medical history. Don’t live in fear of cancer, but do take these reasonable steps against it.

Parting:

Follow the show! www.paulbryanroach.com parent website.

Send us mail: letters@paulbryanroach.com

paul_roach:

One. Hey everybody, welcome to So Is Cancer, a podcast dedicated to being a how-to manual for cancer patients and their friends and families. Each month we will work through different elements of the overall problem, from soup to nuts, as they say, beginning at the beginning, such as the basics of what cancer is, who may be at risk, who's involved in the treatments, why treatments differ so much from one cancer to another. or even within the same type of cancer. The podcast works through various possible outcomes and quality of life issues. Why do we have it? There is a need for a physician-led podcast series that is patient-centric. It helps to have a chat with your physician, only that chat is usually short, emotional, hard to remember, and often only the beginning. Our disclaimer is that this podcast is for informational purposes only and should not be employed for a specific clinical decision-making. For any such efforts, please communicate directly. with your personal physician. Today we are thrilled and excited to have our usuals, Peter Slagle.

peter_schlegel:

Hello, honored to be speaking again on the subject of cancer and would love to talk about what is cancer.

paul_roach:

All right, and Michael Reardon.

michael:

And I'm honored to be here as the voice of the every man.

paul_roach:

All right.

michael:

Thanks for having me.

paul_roach:

Oh, sweet. All right, well, so first of all, guys, how you been? Pete, we missed you during bladder cancer. You were busy doing kid stuff.

peter_schlegel:

Yeah, I'm personally doing well. I'm skiing, I'm outside, I'm enjoying life, just enjoying time with the family. Not working too hard for once in my life.

paul_roach:

That's right. Righteous. Very righteous. Michael, how about you?

michael:

Same old same old over here, Paul. Nothing exciting to report, but looking forward to tonight.

paul_roach:

All right, all right, man. All right, so tonight we're gonna do the subject of what is cancer. We're breaking from our usual format, which is to take one sort of cancer, like cancer of the esophagus or cancer of the bladder, and deep dive into that. Today we're just gonna go onto the subject of what is cancer. And I'm really excited. I've been wanting to do this for a while. I had a patient today, and again, I spent probably 30 minutes explaining to him and his wife what is cancer. So I think that there's a lot of potential for this show. We're gonna have a short definition of it, which is one sentence long or so, and then a long definition, which will be the rest of the show. So Pete, anyone wanna take a stab at a short definition, or should I just go with what I've typed up here?

peter_schlegel:

Well, I don't think there's one definition of cancer. Being a cancer specialist, I could talk about cancer for hours and hours. And I think the most important thing at this point is just to talk about who the audience is. Because if I'm talking to a group of seventh, eighth graders for career night, it's gonna be a totally different audience than talking to my colleagues, surgeons, pathologists and whatnot. On the other hand, I think we're trying to speak to people who are affected or interested. from adult level in terms of what is cancer. And I'll kind of leave it at that and we can charge forward.

paul_roach:

All right, all right. Mike, how much familiarity do you have with this subject?

michael:

just what is cancer in general?

paul_roach:

Yeah, yeah.

michael:

Not, you know, no clinical knowledge and probably like everybody else out there, it's something that I would dread to hear, I guess, is what it kind of what it means to me when

paul_roach:

Got

michael:

somebody

paul_roach:

it.

michael:

uses the word cancer.

paul_roach:

All right, so, you know, a short definition that I pulled out while researching for this episode was that it is a disease caused by an uncontrolled division of abnormal cells in a part of the body. It's a disease in which some of the body's cells grow uncontrollably and spread to other parts of the body. And that's from the National Cancer Institute, their webpage on what it is. But that doesn't, in my mind, help patients very much. So we're gonna go into the longer one. But before we talk about cancer, the first question I wanted to throw out there is what is life?

michael:

Oh, you're kidding.

paul_roach:

Yeah, yeah, I figured let's get started

michael:

How much time do we have?

paul_roach:

at the base. Well,

peter_schlegel:

Hehehehe

paul_roach:

so I was going down that rabbit hole listening to the Lex Fridman podcast. And he had all these astrobiologists and there was a Turkish scientist from university of Wisconsin who was fascinating. Great podcast. I feel a little guilty that I don't buy any of the products that they advertise. I should, you know.

michael:

Well, why don't you put their podcast link in the show notes for this,

paul_roach:

All right,

michael:

and anybody interested

paul_roach:

all right. I will

michael:

can hear

paul_roach:

do that.

michael:

that.

paul_roach:

It's great podcast. Anyway, so a NASA definition, because NASA is looking for life on other planets and so they have to figure out, well, what are we looking for? So they said, life is a self-sustained chemical system capable of undergoing Darwinian evolution. Self-sustained chemical system capable of undergoing Darwinian evolution. All right, that's painful.

michael:

You're really clearing things up for the audience

paul_roach:

Yeah.

michael:

interested

paul_roach:

So,

michael:

in cancer, Paul.

paul_roach:

so then I, then I, I looked, all right, what is the world of philosophy have to say? Because, you know, I had a Jesuit education. I figured better hit that. And that was even worse. So I'm not even going to read that because I don't want to lose the audience right up front. But my summation of all the philosophical is something that dies. So if it could die, then it's alive. Like a rock can't die. But it's tricky, like a virus. Is that alive? Is that not alive? I don't know. It's

michael:

it

paul_roach:

sort

michael:

die?

paul_roach:

of dormant. Yeah. All right,

michael:

Well, if

paul_roach:

so

michael:

it can

paul_roach:

anyway.

michael:

die, then by your definition, it's alive. We just solved a lot of science,

paul_roach:

A lot

michael:

I

paul_roach:

of

michael:

feel,

paul_roach:

science right there.

michael:

tonight,

peter_schlegel:

Hehehehehehe

michael:

right there.

paul_roach:

Who even needs Lex Fridman and his awesome podcast? All right, so question number two. So beginning with what is life? So we're alive, we've got DNA, we are a biological system that has sort of institutional memory. You can pass down one generation to the next and you can keep this thing going. What is a cell? This is the other definition that we have to get into. And I'll put the link. for Cancer.gov on what a cell definition is. But in biology, it's the smallest unit that can live on its own. And it makes up all the living organisms and tissues of the body. So in order to understand cancer, Pete, I was thinking maybe we sort of have to talk a little bit about a cell. What do you think? Ah, ha ha ha ha! Alright,

michael:

What?

peter_schlegel:

Well,

michael:

What? What's?

paul_roach:

we'll

peter_schlegel:

maybe

paul_roach:

keep it short.

peter_schlegel:

I could refocus just a little bit and saying that we're going to have a problem trying to fit what is cancer in the 90 minutes here. And I would have to say that maybe you could start with cancer. Is that the opposite of life? But the perplexing problem is that cancer is living. So how do you account for that? So that probably brings up more. questions and answers.

paul_roach:

Wait, there's a question in the classroom.

michael:

Well, I'd

paul_roach:

Mike.

michael:

like to conjecture,

paul_roach:

All

michael:

if

paul_roach:

right.

michael:

that's a word, is cancer life out of control?

paul_roach:

Exactly.

peter_schlegel:

Excellent.

michael:

Okay, I'm gonna go with that one.

paul_roach:

That is perfect. And that's actually why we brought the whole thing up. So a cell is this organized, it's this organized item and your body has about 37.4 trillion cells in it. Let's just say that's what Mr. Google says, Dr. Google. And there's 37 trillion cells and each cell has. a few parts. It's like bricks, let's say, in a wall, but it's a lot more complicated because there's the outer surface, which is the membrane, and then there's a few rooms inside of it, which are called organelles, these tiny little sub spaces, and they have different functions too. The center of it holds the DNA, and that's the instruction manual to make a cell or to make every cell in your body. And when cancer, when the cell is working, everything's working, it's like a new car engine, but when the DNA goes wrong, then the cell goes wrong, and it starts behaving in a bad way. And when it's behaving in an aggressive way, it might be cancer. Or is that, that's probably not working. I can see Mike's face. and peets.

michael:

I mean, it works in one sense, but as I'm in the role of the audience at home, you're kind of losing me. I

paul_roach:

Alright.

michael:

mean, I get it that the cancer is when the instructions for the cell factory and the cells in your body, they keep renewing, they keep rebuilding. And somehow, somewhere, the instructions, the DNA take a hit, it goes wrong, and they begin... to multiply out of control or they begin to build themselves in a wrong way and then get out of control. But

paul_roach:

That is

michael:

I think

paul_roach:

awesome.

michael:

that's enough.

paul_roach:

Yeah, I think we're almost done. Pete?

michael:

And it just, because at Organelles,

paul_roach:

Yeah, yeah, that's

michael:

I was

paul_roach:

all

michael:

gonna

paul_roach:

right.

michael:

go

paul_roach:

All

michael:

to the

paul_roach:

right.

michael:

kitchen and make a sandwich.

paul_roach:

All right. Sorry about

peter_schlegel:

Hehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehehe

paul_roach:

that. Sorry.

peter_schlegel:

I'll reinforce what you said about the cells. The cells are the basic building block of everything from organs to the whole organism, the whole human body, the whole animal, whatnot. I think drawing back to a little bit about cancer that I look at it in an oversimplified way. And kind of as a biologist, we're talking a little bit about cells. And I think about Cancer is just being bad. The definition of malignant is bad, evil, does nasty things. And what exactly does cancer do? But it's like a weed, and I use this analogy in my head, and I try to explain it to my patients. Also, it's like a dandelion, it develops roots, it can develop the ability to send seeds, and those seeds can be sent forth and wind up elsewhere and grow. And by using the analogy of cancer as a weed, I think it really applies in very many ways. Another example you could say is in what type of soil does it like to fall into? And some cancers that spread have an affinity for the bone, some have an affinity for the liver. You could say, well, it likes to grow in this soil, it doesn't like to grow in that soil and so forth. From a biology point of view, I like to kind of draw back to say, what is a weed and how does it do bad things? And anyway, that's a model that's worked in my brain for a number of years.

paul_roach:

All right, Mike, what do you think?

michael:

I mean, that makes kind of perfect sense to me. The only question I have about that, Pete, is that being the case and having talked to you guys now for four of these podcasts is that that weed can change. You started out with a dandelion and the dandelion has totally taken over my lawn. So I know exactly what you're

paul_roach:

Hahaha

michael:

talking about. But at the same time, I've learned from these podcasts that that cancer, that original dandelion could become thistle it could become I don't know any other weeds but it can become other weeds it can change as it moves throughout your body system so is there something else that's going on or is that just like let's just take the the basic model and let it go from there

peter_schlegel:

Well, maybe I could change the model a little bit and say that some weeds kind of creep along through the root system. And I don't know enough about the plant world to describe like a creeping sort of ivy that just creeps along and the roots just kind of pop up. Alternatively, there are certain plants that the pollen and the seed just get dispersed and spread wildly. And in terms of one organ, yes, they do mutate, but where they wind up, that's really the key of what happens and where they take root. And to think of the soil kind of as your body, and it's trying to support normal growth. And the weed gets in there and interferes with that function, whether it's your bones or your liver, lymph nodes, what not.

paul_roach:

Yeah, you know, I think probably during the course of this, we'll go through tons of analogies, and I think we have to, and we'll draw them probably all from different biological systems. But one of the things that I would like to describe is that, let's say you look at a building. It's an office building. And it's got all different kinds of... construction materials, bricks for the flooring, and then there's lighting and computer stuff or whatever else. And it's sort of... Amazing to think that every animal out there, every plant out there, whatever, it began with one, one, like for a building, like one brick, and then that one thing multiplied and developed itself into this enormous building. And the orchestration of that process and how the thing can change from one type of material to another, to another, in order to create this whole building is it's incredibly well orchestrated. It somehow does it by itself. You know, nobody tells, like my daughter just got a new kitten that things about eight weeks old and it's 50% head and. 50% the rest of it is neck, body, legs, and tail. But how did it become something out of one cell? And the incredible orchestration of that event going from one cell into trillions of them, when that thing starts to go wrong, think of like a top that is spinning and it's perfectly still, and then it starts to lose

michael:

This is

paul_roach:

itself.

michael:

like the eighth analogy.

paul_roach:

We're gonna keep going till we find one that works. But I think that to me, that's sort of the secret of understanding cancer is understanding where have we already been first. So you go from like a single, like once upon a time, Paul Roach, Pete Slagle, Mike Reardon, we were just one cell. That's it, one cell. And then that thing multiplies into two, into four, 16, 64, and it goes on into a ball. And then it turns into a flat two-layered disc. and then the cells keep developing into a three layered thing. called an embryo. And then those three layers are the basic three layer, three sort of construction things that everything's made out of. And then this incredible, this flat three layered thing does origami and it folds into a three dimensional creature. And then, and then all these organ systems develop, whether you're talking your lungs or your heart and vessels or your digestive system or your urinary tract or your skin, your bones and muscles, your nervous system, your brain.

michael:

Here's

paul_roach:

And

michael:

a question

paul_roach:

all of

michael:

for

paul_roach:

that,

michael:

you,

paul_roach:

all of

michael:

interrupting

paul_roach:

that. Yes, sir.

michael:

as I like to do. Is it possible for cancer to develop at that stage? Like can an embryo have cancer? As the whole machine is coming together, is that possible for that to go off the rails right then?

paul_roach:

That is a great question. Now a lot of times when people have a miscarriage, something went wrong early on.

michael:

Okay.

paul_roach:

Pete,

michael:

And it's

paul_roach:

you

michael:

possible

paul_roach:

would.

michael:

that it's that it's what we're going to eventually call cancer, but probably that doesn't really matter in that instance, because it's a miscarriage. We generally

paul_roach:

Right,

michael:

label

paul_roach:

it goes

michael:

it that.

paul_roach:

away. But there are pediatric cancers. Pete, do you ever see pediatric cancers or no?

peter_schlegel:

No, fortunately, I'm an adult oncologist, so I don't see that. But I do agree that the miscarriages often are a result of some sort of genetic malformation or disorder that doesn't lead to life, really. And the body senses that and therefore the child doesn't live and it becomes a miscarriage. We do see some infants with cancer and they tend to be very, very aggressive. But I don't know how that ties into this. Discussion albeit that cancer can really affect anybody at any stage of life.

michael:

just something happens with that machine that we're talking about. And it doesn't really matter. You don't know when that's gonna.

peter_schlegel:

Yeah, well, Paul was talking a little bit about biology and DNA and cells. So the DNA is basically the brains of a cell and that can become mutated. And we have different terms. One of us called the driver mutation where something happens and it drives this cancer, this cell to become cancerous and there's oncogenes. And there's a whole bunch of fancy terms that we can throughout, but the basic line is that DNA gets twisted and mutated, and that leads to this abnormal growth. What I think is interesting when we start to talk about mutations is that the environment can influence those mutations. If you look at somebody who is a smoker, that they start off, have a couple of cigarettes, their lungs become red and inflamed over time. the cigarette smoke leads to mutations, atypias we call it, some benign tumors. And then as this process continues, the body becomes more and more inflamed and agitated and the DNA becomes more twisted to the point that it becomes cancer and it just starts growing on in infinity. And we had talked a little bit about how cancer is actually living and how it picks up these mutations and. grows out of control.

michael:

So, but a mutation itself isn't necessarily a bad thing, right? I mean, I have blue eyes and that's a mutation that occurred many, many millennia ago. But, so what's the difference between basically a mutation and a cancer?

peter_schlegel:

Yeah.

michael:

Is it?

paul_roach:

Outstanding question. So That alone, I think, Pete and I are both like taking a deep breath in, because that one question could be something that we talk about for a long, long time.

michael:

I'm just going to claim victory for tonight then.

paul_roach:

I think just

peter_schlegel:

I'm

paul_roach:

claim

peter_schlegel:

going to

paul_roach:

victory

michael:

Mic

peter_schlegel:

go.

paul_roach:

for

michael:

drop.

paul_roach:

tonight. But I think if I was gonna try to summarize it quickly without another half dozen analogies, is that a mutation might happen and the vast majority of them that do happen are probably inconsequential. But when the mutations happen in any of the mechanisms of the cellular machinery, that are responsible for signaling and for growth and for that cell sort of growing into what it needs to be. Sort of that cell has a little puberty phase too and it grows into from being a brand new cell into the cell it has to be, whether it's a skin cell or a liver cell or whatever, that's called differentiation. So. When the mutation happens in that process, the cell signaling or its growth, its cell cycle or its growth, that can set up a bad series of events.

michael:

So this is that chain reaction where it's out of control,

paul_roach:

Yeah,

michael:

as

paul_roach:

yeah,

michael:

opposed to

paul_roach:

so.

michael:

a mutation which is still essentially, it's just a change, but it's still under control.

paul_roach:

Yes, yeah,

michael:

Okay.

paul_roach:

you got blue eyes, you got brown eyes. It really doesn't

michael:

Doesn't

paul_roach:

matter,

michael:

matter.

paul_roach:

right,

michael:

Well,

paul_roach:

but.

michael:

it helps.

paul_roach:

Yeah, it does.

peter_schlegel:

Ha ha ha ha.

paul_roach:

Those are some beautiful blue eyes, Mike.

michael:

Thank you. I was

paul_roach:

Yeah.

michael:

waiting for someone to say so.

peter_schlegel:

Well, to build up upon some of the principles we talked about about mutations and uncontrolled growth, that you can have one cell in the skin that mutates and develops this cancerous behavior, and it becomes something called squamous cell skin cancer, basal cell skin cancer. And it tends not to do very much except grow slowly and almost like a barnacle and has to be taken off. However, In rare cases, it can mutate and have additional problems such that it can cause left light threatening illness. On the other hand, if you take the pancreas and you develop some mutations in there, that cancer can grow and become quickly lethal. Even though the same of the biological principles apply, it's just within a different context and a different cell and different mutations that can lead to vastly different outcomes. And

michael:

Well, it sounds

peter_schlegel:

that's

michael:

like

peter_schlegel:

it.

michael:

you're talking about the soil that you were talking about earlier with the dandelion analogy, that the soil that this lands in, these seeds land in. So if it lands on the skin, potentially it's slower. If it lands in the pancreas, it's potentially a fast growing, fast changing, much more life threatening change. Is that correct?

peter_schlegel:

It's a little bit off in terms of how I explained it. The cell of origin in a skin cancer, generally the skin, and if it becomes cancerous, well, it still grows, but this dandelion might be different than another subspecies of weed that develops in the pancreas. And it kind of comes back to the DNA mutations and how aggressive the mutation leads the cell to. and there are certain patterns that are predictable. There's a type of leukemia called chronic myeloid leukemia. It was one of the favorite cancers to learn about in medical school and residency because it's caused by a precise mutation from the ninth chromosome to the 22nd become fused. They become glued to each other in a way that controls uncontrolled growth. So it's a kind of a pattern that human beings have and why that... specific mutation happens were not exactly clear, but it does, and it happens at a pretty low, but reproducible level. So it has a lot to do with the cells in this chronic myeloid leukemia example. It was in the bone marrow. On the other hand, these other sort of cancers in the skin, that the mutation can occur elsewhere, but they're just not as. Whatever happens doesn't have the stereotyped bad behavior that the leukemia can have.

paul_roach:

It's a really interesting problem. For example, in the skin. The, we just had the podcast, two podcasts ago on melanoma or maybe three. And so that cell, which is for the most part located in your skin, there's some located in your retina and a few other spots, but for the most part, it's in your skin. That cell, when it decides to go bad, it typically becomes very dangerous, very fast. Whereas, when the other cell, the epidermal cell on your skin goes bad, it doesn't, it'll grow and become a problem locally, but it is not the type of thing to move to your lymph nodes or to the rest of your body. It's just two very distinctly different behaviors.

michael:

Are we talking about benign tumors versus

paul_roach:

Actually,

michael:

cancerous tumors?

paul_roach:

no, these are both

michael:

No?

paul_roach:

cancerous.

michael:

Huh.

paul_roach:

They're both cancerous, but there's a big broad variability in how they behave. And so that's probably maybe the most dramatic difference. The basal and squamous cell only rarely will become metastatic, but the melanoma cell will frequently become metastatic, even at a fairly early stage.

michael:

And that just

paul_roach:

will.

michael:

comes back down to what instructions in the cell machinery

paul_roach:

Mm-hmm.

michael:

were damaged or changed.

paul_roach:

The biology, my pet theory is that the melanoma cell is so quick to metastasize because that's how it got there in the first place. That would be a long discussion, but it comes from this, its original source isn't the same as those other cells. It's from neural crest, not from the... epidermis and so it migrated into there to begin with. And so that's my pet theory of why it's so quick to metastasize is it's already done at once. But like Pete's other example of the pancreas, nearly all the tumors that happen in the pancreas, let's say there's a half dozen typical ones, most of those are just awful. And they all behave in a very aggressive way. And it's also even worse, it's compounded. When you have a cancer on your skin, you can see it and you can feel it. But in your pancreas, it's in the center of your body and you don't know it's there.

michael:

I know that, I mean, I've had a couple of people that are friends of mine that have died from pancreatic cancer and it, within months of their diagnosis, like very, very rapidly within weeks and one case, I think, is that again, just that person's individual sort of their genetic code, their instructions are the change hit it at like high speed. And that's what's happening? Or

peter_schlegel:

Yeah, exactly.

michael:

is it...

peter_schlegel:

The cancers that develop in the pancreas tend to be very aggressive, so they grow very quickly, and they have some of the malignant characteristics. They develop fingers, and we technically call those invasive component, as well as spread or break off and metastasize. Not only does the cancer have to have the ability to break off, it has to have the ability to stop somewhere and to have a... soil sufficient for growth and then it can grow from there. And typically the pancreatic cancer nests in the liver, which is a vital organ, and that's usually the end result of terminal cancer.

michael:

Okay, just to clarify, when you say fingers, we're really talking about roots or branches, right?

peter_schlegel:

Correct, yeah, just

michael:

Because

peter_schlegel:

like the

michael:

I

peter_schlegel:

dandelion

michael:

know from the...

peter_schlegel:

I was saying. And that's what makes it so hard for Dr. Roach to do a resection of a pancreatic cancer. You don't know where to stop taking out the roots. And if it's a colon, well, who cares if you take two inches of your colon or six inches. If it's really bad, you'll get a colostomy, you'll take more of it. But in the pancreas, it's just such a tight little area between the small intestines, the liver, the bile ducts, some major arteries that innervate that. circulate blood into the intestines, that it's very complicated to get in there and get it all out and then put the patient back together.

michael:

Once the cell machinery starts to degrade and the instructions are going haywire and you basically have cancer, this kind of comes back to some of the things we were talking about before. How detectable is that? I guess this is different for every cancer. Is it something that can be kind of quickly, like... seen? Is it something that can... I think I'm answering my own question because

peter_schlegel:

Yeah,

michael:

I'm thinking back to skin

peter_schlegel:

that's

michael:

cancer.

peter_schlegel:

a great question in terms of if I understood the question correctly regarding diagnosis and, you know, when our cancer is diagnosed, when are they sensed by people and when do they raise it to attention to their primary care provider or some other healthcare professional. If you have skin cancer, you see something growing on there and say, well, you know, this does not look normal. I got to get this off. On the other hand, with pancreatic cancer, It can be pretty insidious and cause abdominal pain and who's not had some heartburn or a little indigestion, dyspepia, some colonic issues, and we just kind of live with that. Question is when to pull the trigger and say, hey, doc, I got a problem, please take a look. And it's not like the doctor can just wave a wand and say, hey, you're good, you're bad. He or she has to order a CT scan or do an MRI or something that's expensive, time consuming. takes a lot of effort to figure out.

michael:

So there are not very

paul_roach:

I think

michael:

many

paul_roach:

that...

michael:

diagnostic tests that just sort of quickly and easily check for just any kind of quick abnormalities that might suddenly be happening, right? Like

peter_schlegel:

Yeah,

michael:

there's

peter_schlegel:

they've

michael:

no...

peter_schlegel:

got...

paul_roach:

on Star Trek,

michael:

Well,

peter_schlegel:

I'm going to go

michael:

the

peter_schlegel:

to

paul_roach:

on

peter_schlegel:

bed.

michael:

reason

paul_roach:

Star Trek,

michael:

I say

paul_roach:

he's

michael:

this,

paul_roach:

got that thing.

michael:

the tricorder. Thank

paul_roach:

Yeah,

michael:

you.

paul_roach:

but, but here, no. And one of the issues, and I want to get into this is, cause it's a perfect, it's an outstanding question, is cells are really small and cancer can begin with one, one single cell. And a cell is, I don't know, 20 microns wide or something like that. It's a micron is 10 to the minus six

michael:

Yeah,

paul_roach:

of a

michael:

you're

paul_roach:

meter.

michael:

losing. You're

paul_roach:

Yeah.

michael:

losing those norms, those normies.

paul_roach:

Okay, sorry. It's to sort of quote, who's

michael:

smaller

paul_roach:

the

michael:

than

paul_roach:

guy in Zoolander, Derek,

michael:

Zoolander.

paul_roach:

Derek Zoolander, yeah. It's really, really, really small, right? And So a cubic millimeter has 100,000 cells. And 10 cubic millimeters has 100 million cells. So what happens is you get one cell that goes wrong and 20 generations later, that is 10 millimeters. It's about the tip, your pinky tip, that little box. about your fingernail and the fingertip on your pinky finger. That's, let's say, a cubic 10 by 10 by 10 box of 100 million cells. So that's 20 generations. 10 more generations from 20 to 30, that thing is now 10 centimeters by 10 centimeters by 10 centimeters, which is like the width of your hand in three

michael:

All right,

paul_roach:

dimensions.

michael:

a couple of versions back, podcasts you were talking about grapefruits. And we had the grapefruit size this generation.

paul_roach:

Yeah, at that point you're near it. And anything that big is enough. Any 10 by 10 by 10 volume of cancer is enough to drop an adult, typically.

michael:

So

paul_roach:

If you have.

michael:

when you go back to the pinky size tumor,

paul_roach:

Yeah.

michael:

is that basically when it becomes

paul_roach:

detectable.

michael:

detectable? OK.

paul_roach:

Right, and so that's 20, that is 20 generations

michael:

from the first problem.

paul_roach:

from the first one and only 10 more generations and it's the width of your hand times three dimensions. You know, so by the time you detect it, it's already two thirds of the way to the finish line. So that's part of the real challenge. That's why we do things like mammograms or for people who are smoking, they do the... Now it's new, the low dose cat scans of your chest, you know, and skin checks for people and colonoscopies. But

michael:

Well,

paul_roach:

you

michael:

right.

paul_roach:

have

michael:

And

paul_roach:

to

michael:

I guess that's what I was questioning is, where is the science in terms of getting us kind of almost a universal test or at least a test for specific cancers like a colonoscopy. I actually saw a Ted talk where this teenage kid invented like a $3 test to detect early pancreatic cancer because someone that he loved, he was a high school student and he figured this out. Where is the science on that? Like how far are we in developing more tests that can detect cancer earlier, or really are we at the kind of the mercy of the speed at which it's being programmed to run?

peter_schlegel:

I think the biggest success that we've had is cervical cancer. When women go in for their pap smears or annual gynecological exam, it usually includes an evaluation of their cervix. And often what they do with the pap smears, they take a little biopsy, a smear of the cells there to see if there's any kind of premalignant cancer cells there. And I'm not gonna go into all the details there, but that's the basically idea of pap smears is they can detect pre-cancerous areas and that will heighten awareness that there could be a problem. And so that if you, so that the vast, vast majority of women who are being screened will not die from cervical cancer. They may be diagnosed with cervical cancer or some pre-cervical cancer form, but they won't die of it. If you look at breast cancer, we've had a lot of success and about nine out of 10 women ultimately survive their breast cancer. We can still do better because one out of 10 are dying from breast cancer. But that usually has to do with mammography and early detection. So if a woman notices a small area on her breast or she gets her yearly mammogram and they find something, the outcomes tend to be much, much better with early detection. The last example I'll give is prostate cancer and a lot of men will undergo PSA screening. And as a result, we've seen the number of cases of death from prostate cancer over the last 20 years or so basically drop in half. That's not to say there's not lots of surgeries going on, lots of biopsies, lots of trauma and complications of those treatments to rid men of their prostate cancer. But. We've likewise seen a huge decrease in the number of people dying because of early detection. And going back to, you know, which cancers have we had success with? Those are a couple I can maybe list about two other ones. But things like pancreatic cancer, it's just too hard to make that diagnosis.

michael:

Well, I'm going to jump back in on you then because I know I saw the TED Talk. So I did a quick Google while you were not talking. I was paying attention.

peter_schlegel:

Hehehe

michael:

paul_roach:

No, I didn't go to that kid's grade school.

michael:

No, shut up!

peter_schlegel:

Hahahaha

paul_roach:

There's always some parent is doing the science fair.

michael:

Oh, this kid, I saw him, he spoke on a TED Talk, and I like TED Talks. And I guess what I'm saying is, that's what I'm looking for is ways for this type of early detection to happen. But if you two who are oncologists didn't hear about it, then there's a disconnect, there's a break in our system of how we get the information disseminated and how, I mean, that thing may still be in development, I don't know, but he figured it out.

paul_roach:

I think it's awesome. I mean, I know there's dogs that can sniff and tell if there's lung cancer.

michael:

I don't

paul_roach:

You

michael:

know,

paul_roach:

know,

michael:

why

paul_roach:

like

michael:

isn't

paul_roach:

the

michael:

there

paul_roach:

bomb

michael:

a dog

paul_roach:

sniff.

michael:

at my doctor's office then? Like, why am I not just being tested? Why are we everymen? As I'm, you know, putting on my everyman cape. Why are we not going into our doctor's office and getting, uh, as, as early a test on everything as we can. And,

paul_roach:

So

michael:

and

paul_roach:

that also though is, it is a little more complicated than it might seem. So it's a very good question and very legit and like if this kid's pancreas project actually works, then we should all adopt it, that sounds awesome. But for example, like the bladder cancer episode last week, why don't we stick a scope in everybody's bladder to see if they have bladder cancer? Well, the problem is

michael:

The test itself

paul_roach:

the

michael:

causes

paul_roach:

utility

michael:

a problem

paul_roach:

of

michael:

is what

paul_roach:

doing

michael:

you said.

paul_roach:

that. Yeah. And it's also dependent on how prevalent it is in the population. So for example, like my good friend, his wife recently passed away from lung cancer. And the same question, you know, geez, we get skin checks, we get, you know, cervical cancer checks, we get breast cancer checks. How come this wasn't picked up? People did try screening everybody with chest x-rays for lung cancer, because lung cancer is so common and it's so bad. And it, it really just didn't work because it caused a lot more trouble than it solved. Because when you do the x-ray, you see a blip and then you don't know what to do with the blip. Does that make sense?

michael:

Yeah,

paul_roach:

And you,

michael:

the

paul_roach:

you chase

michael:

false readings.

paul_roach:

them down. Yeah. You chase them down and you biopsy them. You cause all kinds of problems. and you still miss a lot of the cancers. Now, only recently, what we've done is we've refined the population of adults who should get lung cancer screening, and for the most part, it's people who have smoked of a certain amount over the course of their life, and then once a year, they go and they get a low dose CT scan of the chest, and then you can identify those things. We just instituted that program at our hospital. I was part of the group. doing that and we've caught a few lung cancers at an earlier stage already, even in just like the first five months of this thing. So.

michael:

All right, so Pete, it's the same thing happening kind of in your world too, that there's a move and a push and a desire to move things into an early detection as possible.

peter_schlegel:

That'd be great. But in the real world, it's hard to talk people into getting colonoscopies. It's hard to talk men into getting PSAs. It's hard to talk women into doing mammograms for another 10 years after they've been doing them since age 50, and then they say, you know, they're always negative, so why should I bother doing them anymore? It's something that has become particularly difficult with the COVID and things that have happened to the healthcare system. of the last three years.

michael:

You

paul_roach:

One

michael:

saying

paul_roach:

thing.

michael:

like the more common and routine it becomes, the less people sort of buy into it? Like it's eh.

peter_schlegel:

paul_roach:

But there's an ongoing search and it's a big one for tumor markers and identifiers. You know, there's a thing coming into play now called the liquid biopsy where, you know, let's say I had a colon cancer and, or a prostate cancer or a lung cancer, and I was treated or a thyroid cancer, and it all went away. Then you can draw some blood and check a marker and see if it's come back. without having to go through the whole scan and everything. And that.

michael:

Does that happen every time I go to my doctor and they draw blood? Are they testing for that?

paul_roach:

Negative. This is only under very specific circumstances and it's the more sophisticated versions of that process are still very much under development. So that's something that, let's say, our children, when they're our age, perhaps they'll be able to do. But we're nowhere near there at the moment as far as I know.

michael:

So we're still at the level where you're going to, you almost have to have a tumor that's developed to that pinky tip of your finger size before it can really sort of be detected and you guys can

paul_roach:

Yeah,

michael:

see it and work with it.

paul_roach:

but it also begins, you know how one theme is we always end up saying you have to go to your primary care doctor and give him good information or give her good information. And it begins with that. If you're like, I, you know, I'm gonna confess, I did a lot of tanning beds in my, you know, past

michael:

your

paul_roach:

20

michael:

youth.

paul_roach:

years. Yeah, they're gonna do a real close skinny, skinny vow. And you're gonna be on a. Whatever, if you're like, ah, I smoked a lot, boom. Or a number of people in my family have had stomach cancer, isn't that weird? Boom, they're gonna check that out. Or you tell them about your breast cancer or whatever. Or, oh, I just had some blood in my urine. I don't know what happened. So that's where it sort of begins. And then your physician can do a targeted check on that area.

michael:

Okay. You just sort of touched on a lot of people in my family and that's a genetic predisposition towards a specific kind of cancer. Can you guys give me any breakdown or any insight into what that kind of entails?

paul_roach:

Well, every time I meet somebody, I ask them, for the first time, has anyone in your family, even if they're there for a groin hernia or whatnot, I just throw this out there, anyone in your family have any important medical problems? And they usually say, dad had high blood pressure, mom had a heart attack, whatever. I always ask since I'm interested in cancer, I say, any cancers running through the family? And if they say, Sometimes there's a number of cancers that different first and maybe second degree relatives have had. If they fall into certain patterns, that makes me think of cancer syndromes that can be passed on from generation to generation.

michael:

Well, let me pull this back around to where we started with what is cancer. How is it possible that, you know, you can live to be 50 or 60 years old before the instructions are there, that the genetic code is there already? Why does it take 60 years before that machinery goes bad? When the instructions start to start to overpopulate and get out of control.

paul_roach:

Oh, let's let Pete take this one.

peter_schlegel:

Well, every year you get older, your machinery gets a little bit older and a little bit more susceptible to a mutation, degradation of the DNA and mutation that leads to cancer. Certainly the first time you smoke cancer, your risk of lung cancer is essentially zero. But after 80 years of smoking, you're most likely going to have lung cancer and just life. causes problems. They're just a baseline level of mutations that occur. I think some of the other details are lifestyle can make a big difference, your immunity can make a big difference, other health problems, etc. etc.

michael:

Yeah, but specifically genetically, like if my, uh, He didn't, but let's say my father had skin cancer. Actually, he might have. Now, think about it. If my father had skin cancer, and there's a genetic predisposition that Paul asks me, and I said, well, five people in my family have had skin cancer, but they... probably a bad example because

peter_schlegel:

Yeah,

michael:

I know

peter_schlegel:

my

michael:

that's

peter_schlegel:

B!

michael:

really caused by an outside thing. If I have a genetic predisposition for a specific cancer, but the instructions are there when I'm born, why didn't I get it within a year? Why did it wait until

paul_roach:

Ah!

michael:

I was 65? Yes, Paul.

paul_roach:

All right, okay. So, let's say it's about 15% of breast cancer, for example, because it's very well studied and very well known, is heritable, meaning it's part of a family trait that comes down through the generations. It's not random. And the most common genetic abnormalities in that scenario would be the BRCA1 and BRCA2 genes. Does that make sense? Have you heard of Bracca? Okay, like the Angelina Jolie problem or.

michael:

That's Brangelina. What's Branca?

peter_schlegel:

Yeah.

paul_roach:

Okay, all right. So BRCA is a gene and and there's two BRCA number one and BRCA number two and these two aren't too structurally similar but they both kind of do the same thing which is they're they're part of the DNA repair machinery. Believe it or not in every one of your 37.4 trillion cells every single one You've got little machines in there whose job it is to fix the DNA when it breaks, because it breaks through normal wear and tear. And you have little machines in each single cell that fix it. Now, if that doesn't blow your mind, anyway, it's amazing. Well, the BRCA1 and BRCA2 genes both are involved in this DNA repair process. And when they are out. Let's say you're born with a defective BRCA1 gene. Then the DNA repairs throughout your life aren't fixed as well as they would have been. and you're at a higher risk.

michael:

But starting from the beginning of my life,

paul_roach:

Yeah. Yeah. And so.

michael:

it's doing an okay job,

paul_roach:

but not a great job.

michael:

but not a great job.

paul_roach:

Yeah, because the BRCA gene is not working. And so over the course of your decades, you have a higher risk of breast cancer, a higher risk of bilateral breast cancer. And it just so happens, it means something to Pete and I that it's a higher risk of triple negative breast cancer, which is a certain type. And... And that's just, you sort of got a head start on it, but it isn't guaranteed. It's only, let's say a 60% chance, or maybe it's 40%. I don't know, remember off the top of my head what the lifetime risk of breast cancer is, but you also have a higher lifetime risk of ovarian or endometrial cancer as well. Or if you're male, you might have a higher risk of the aggressive version of prostate cancer or of pancreatic cancer,

michael:

And these

paul_roach:

you know.

michael:

are from the same defective VRC.

paul_roach:

Yeah, exactly. And so it's only loading the dice. It's not a cancer, for any one cancer, there's typically 20 genes or something that are defective. It's not just like, oh, one bad one. It's a group, it's a group. And there may be a usual suspects list of 200 genes or whatever, but. For any cancer, it takes a lot of different genes being out of functional order in order for that cancer to happen.

michael:

Okay, and then Pete, kind of what you were saying to me a minute ago, which is there's also environmental impacts that can happen. Is this then working in combination where my already kind of damaged DNA from birth meets environmental factors that then worsen my odds, as Paul is saying? So it's almost like it's a loaded, it's a loaded gun, or it's a match waiting to be lit.

peter_schlegel:

Exactly. That if you have a woman who has a genetic predisposition, she's already got one mutation, and then you add like estrogen after menopause that could increase and drive the mutations even further. People who have predispositions from lung cancer and they smoke that that will increase the risk if they've had other environmental exposures to different toxins and gases and things like that.

paul_roach:

Yeah, these things add up, like Pete's saying. Let's say I work with asbestos, and I'm not perhaps using whatever that gear is that they have to use. If I don't smoke, my risk of lung cancer or mesothelioma, the type of lung cancer associated with asbestos, is X, whatever it is. But it's not, I don't believe it's that much higher. But if I do smoke, it's way higher. you know, the two together amplify one another very significantly.

michael:

So then would you guys recommend kind of understanding where you are at risk on a baseline by getting like a 23andMe genetic test done that kind of tells you what your genetic predisposition is towards something like that?

paul_roach:

All right,

michael:

Like

paul_roach:

so.

michael:

would that be useful to you as doctors to know that I did that?

paul_roach:

This is another awesome question. So you're full of them. You're really like batting

michael:

I'm gonna

paul_roach:

400

michael:

roll.

paul_roach:

tonight. Yeah. So the problem with genetic testing, and I'm sure Pete's been through this too, is it's extraordinarily powerful information. And sometimes people... get their genetic results. And I was in this situation just like a month ago. Somebody ordered it for a patient. They didn't have any idea what was really at play. They'd given the results and it happened to be BRCA positive. And then the person comes into my office and was extremely upset because everything was dawning on her all at once. And it just wasn't the right way to go about it. because it's super powerful information. If you have BRCA, that means each of your children has a 50% chance of carrying it. So now you're dealing with this young person who suddenly this heavy duty info is just dropped on their lap, and then they start thinking about their kids, and now it's like quadrupled, you know, the stress, and oddly enough, she described a sense of guilt of having passed it on to her kids.

michael:

But isn't it

paul_roach:

And

michael:

better

paul_roach:

so...

michael:

to kind of have that base information, even though it can be hard to carry? I think there was an actor, who's the guy who plays Thor, just like this month, he found out he has predisposition to Alzheimer's. And so he kind of backed out of a series or something.

paul_roach:

Oh, wow. Yeah, but this is really hard info. And so I think it should be managed not through 23andMe or whatever. I think that if you're gonna get genetic testing, you should talk with your doctor, you should talk about the implications of it, see if it seems to be indicated, and be mentally and emotionally prepared for that info before it lands. It's a lot

michael:

Yeah,

paul_roach:

better.

michael:

but I mean, I guess I keep going back to, I wanna know if there's something wrong with me as soon as possible. And if what you're telling me is, if I have a genetic predisposition towards a failed gene, and if I couple that with some kind of outside environmental factor, that I can really run a risk. So if I know that I've run like a high risk for... I guess, well, you smoking because that's all I know. But if I know that I have this genetic predisposition towards whatever gene would help trigger that, it might keep me from smoking, right? It might keep me from working in a coal mine. It might keep me from other risky behaviors in the environment. Is that like, are you saying basically don't live your life that way? you know, kind of back off and let life naturally unfold.

paul_roach:

What do you think, Pete?

peter_schlegel:

These are excellent questions and there's not easy solutions. I wish that we had some magic scan. The closest one we have is called the PET scan. We infuse people with radioactive sugar and 45 minutes later, we scan them and look for their radioactivity and it'll detect areas that are, we call metabolically active or digesting sugar. Traditionally, cancer should eat up sugar. but they're highly expensive, they expose people to radiation. And in fact, radiation can induce cancer of itself. Some of these genetic mutations will drive people crazy. Some people will take them very seriously and act appropriately. Other people have excessive anxiety and worry, and other people will just disregard it altogether and be in denial. And so, you know, when you do have a strong disposition, I think the proper mechanism is to inform your physician. And often we send people to genetic counselors to kind of look at, you know, what kind of things can we look at? What is the science behind this? What are some of the interventions that can be made? What are some of the screening tests that can be made? And then to move from there. Genetic testing is extremely powerful, but it's a two-edged sword because it might give too much information. And not to say that as someone who believes in science, but we are at a point in science where sometimes it outpaces wisdom and just common sense really.

paul_roach:

And there

michael:

Is

paul_roach:

are

michael:

there

paul_roach:

a lot

michael:

a genetic?

paul_roach:

of genetic items that nobody knows how to interpret.

michael:

Oh, well,

paul_roach:

Like.

michael:

I guess that does lead to my other question, which is, is, you know, I'm talking about 23andMe, which I know does a medical screening. That's not what you guys are using. What's the genetic test that you guys are ordering? Is it just incredibly more powerful? Is it more invasive? What does that entail?

peter_schlegel:

Well, first of all, the test, we can order them on what they call the germline and that's kind of what you're born with. And then you can do a mutation analysis and a lot of advanced cancers. We wanna know exactly what's going on in the cancer cell so we can predict its behavior. And more importantly, that we can offer treatments against that specific mutation. We call that a driver mutation or a targetable mutation so we can use a certain intervention to go after that. Yes, the genetic analysis and screening is an extremely important tool, but we're just kind of at the infancy with it.

michael:

So the genetic tests that you guys are ordering, they're specific to specific cancers?

peter_schlegel:

Yeah, generally,

paul_roach:

Oh yeah.

peter_schlegel:

if you do have a family history of prostate cancer, you go down one road. If it's gastric cancer, you go down another. If it's colorectal cancer, it's another. If it's breast cancer, you go through another.

michael:

So you're not recommending that someone like me goes out and gets the full bore, you know, 23andMe thing and I come back and I'm like, doctor, I've got 12 different predispositions. What can you do for me? Is that something that you actually see that people are bringing that into you now?

paul_roach:

Yes.

michael:

Oh.

paul_roach:

Yeah. And you know, and I'm like, so we, I will frequently send, let's say a person comes in and they've got a family history of multiple breast cancers or stomach cancers or whatever that I'm concerned about. I will typically not order that the genetic tests for the prediction of future cancers myself. I'll send that person to a genetic counselor. The two of them can go over the family history very, very carefully, and then the genetic counselor will order the very specific tests that apply to that person, that family. Now, break, break, different scenario. I have a patient and she has a breast cancer, and we send that to the laboratory. There, we're gonna... tear that little breast cancer apart, looking for genetic defects, and see which of the four basic buckets or categories of breast cancer it falls into. It used to be that what you did is you took the cancer out and you put a slice of it under a microscope on a slide, and you looked at it, and you made all your decisions based off of that, and. and based upon how locally or not advanced the thing was when you were in the operating room. Now, we go further. We don't just look at that slice of tissue under the microscope. We go into the cells themselves and we look for the genetic signatures. And based on those genetic things, on the hormone receptors, on the presence or absence of something called HER2, and the presence or absence of a few other genetic markers, you can tell an extraordinary amount from it. There's an off-the-shelf type of genetic test called Oncotype DX, which examines, what is it, Pete? 17 different things.

peter_schlegel:

What do we tell you?

paul_roach:

And based upon that, it can give a score. And that score can help you decide if you're going to use chemotherapy or not. So We break it down and breast cancers will typically fall into one of four groups, luminal A, luminal B, HER2 enriched and triple negative. And based on which of those groups it's in, and that's all from cracking the cells open and looking at the genes on the inside and the self-surface receptors on the outside. Based on that, you know, oh, this person can respond to just tamoxifen alone, or that person's gonna need Adrian Mison and Cytoxan, or this person's gonna need this plus that plus the other thing. This is more Pete's line of work. But yes, so there's the genetic studies we can do with somebody who has nothing wrong, but they've got a family history and we're trying to figure out if they have a higher risk or not. And then there's the genetic studies we do on the tumor itself once it's out. So two different sets of genetic studies.

michael:

All right. And so that would sort of dictate a patient response then, right? Like if I if I do it myself or if I know that I've got a family history, I should take it in stride as this is a general bit of information and I should not smoke. I should exercise. I should eat better. I should talk to my doctor kind of in the general health category of with that kind of information from that genetic

paul_roach:

Yeah.

michael:

pretest. But

paul_roach:

So globally,

michael:

then you know, now go ahead.

paul_roach:

yeah, oh, sorry. Globally, this is from a cancer book I was reading. It was estimated in the book, 20% of all cancers globally have to do with tobacco smoke. And then in another chapter, it was something like 20, maybe even up to 25 or 30%, we'll find out over time, of cancers are significantly impacted by obesity. That is not something that we're really talking about these days, but we will be in the future. So those are sort of outside factors. And then I don't know what the exact number is, but let's say 15% of the cancers out there have a strong component of heredity. Do you think that's a fair number, Pete? Or do you think I'm wildly off?

peter_schlegel:

Well, there definitely are modifying factors. And even if someone has a familial predisposition, it might be that they all share similar risk factors, that they all like to overindulge in eating or drinking or even tobacco use

paul_roach:

Yeah.

peter_schlegel:

of

paul_roach:

Yeah.

peter_schlegel:

that matter.

michael:

Or they

peter_schlegel:

Yeah,

michael:

might work in the same line of work.

peter_schlegel:

you

paul_roach:

Yeah.

peter_schlegel:

know, right.

michael:

Okay.

paul_roach:

Yeah, there are toxicology type causes of cancer as well, from the factory exposures and whatnot that are important.

michael:

Alright,

peter_schlegel:

Love

michael:

so...

peter_schlegel:

you!

paul_roach:

And then I think the other thing that's the biggest factor is just simply birthdays. As we get older, like Pete said, the machinery is getting older and more and more errors are made and less of them are caught. And so as you move into your 50s and 60s and 70s, it is increasingly important to just maintain that relationship with your primary care doctor. and do the usual tests that you do for screening and also, you know, take good care of your health and talk with them if you're having any unusual symptoms.

michael:

Well, see, no, for me again, I'm just going to be this guy. I'm now in my 50s. And if I go and get I haven't done it, but if I go and get that general 23 and me genetic test or if I go back and I look at, you know, here's here's what happened to my dad. Here's what happened to my uncle. Doesn't that kind of help me? And not I don't want to go crazy about it, but it would just help me keep informed and kind of keep an eye on like, wow. yeah, obesity was a problem and it may have contributed to some of these later cancers. Or as I get older, there's other things that might be contributing I should watch out for. Like just again, just for general, not going over anxious about it, but general health information. Would you prefer I not do that? Or do you think it's an okay idea?

paul_roach:

I think it's okay. Like Pete said, personalize it. For you, it might be a good idea, but for your neighbor who might be prone to obsess over things and take something that maybe is a small risk and then worry about it all the time,

michael:

I was

paul_roach:

what

michael:

just

paul_roach:

is

michael:

thinking

paul_roach:

it?

michael:

that if I knew, I would know what to tell my doctor. I'd be like, hey,

paul_roach:

Yeah.

michael:

you know what? I have these predispositions and I noticed that my, you know, whatever, my thumb twitches funny. The doctor can laugh at me for that, but I would at least be looking at the right things, right?

paul_roach:

Yeah, I think that's a fine way to go, but I would encourage you to do it in

michael:

grain of salt.

paul_roach:

discussion with your physician, because these reports, first of all, I don't know how accurate the 23 in me is. It may turn out that it's quite accurate. I wondered, is Wikipedia accurate? And then I saw something that said, yeah, it is. But...

peter_schlegel:

Hehehe

paul_roach:

You know, the 23 and me might be quite accurate, but I don't know, we

michael:

Well,

paul_roach:

don't use that in the hospital.

michael:

yeah, right, right.

paul_roach:

So

michael:

So,

paul_roach:

I wouldn't

michael:

well,

paul_roach:

want

michael:

that's,

paul_roach:

you

michael:

you

paul_roach:

panicked.

michael:

know, I guess that's part of the question is, you know, cause I know there was a TV commercial out at one point in time where people were, where Dr. Google says, and the doctors were being driven crazy by this. And I'm sure this has happened to you, where I think my thumb is twitching and I look it up on Google and I come in and, Dr, I've got... You know

paul_roach:

Yeah.

michael:

what, I can't even imagine what I've got, but

paul_roach:

No,

michael:

I've

paul_roach:

mom.

michael:

got thumbatociosis.

paul_roach:

Yeah, mom, you do not have testicular cancer.

michael:

I'm

paul_roach:

Yeah.

michael:

out.

paul_roach:

Even though she looked it up on Google.

michael:

So how often

paul_roach:

Yeah.

michael:

does that sort of happen with you guys where it's become problematic, where it's Dr. Google or it's Dr.

peter_schlegel:

Yeah.

michael:

23andMe or, you know.

paul_roach:

Not too bad for me, how about for you Pete?

peter_schlegel:

Well, from a medical oncologist's point of view, there are a lot of people out there suffering greatly and the medical system does not address everything. And people have bad outcomes and they're desperate. They want something to work. And there are people out there in the United States of America that love to sell stuff and they'll be able to fluff up anything and make a story about how this new immunotherapy this night, this new colonic, this new herb, this new ozone therapy, whatever is going to be the cure-all for their cancer. So there are lots of quacks, there's lots of people selling snake oil out there. On the other hand, there are some useful things available, and it's particularly lifestyle, that people really underestimate just the basics in terms of good sleep, good diet, exercise, having a community, just the basic things that are often overlooked when you're talking to a physician about their cancer and things that are really neglected in many people's lives these days.

michael:

Okay. And not to bring any lawsuits down upon us, we're neither condoning nor denying 23andMe or any other genetic testing

paul_roach:

Alright.

michael:

or anybody else. That's basically saying any information that you have certainly could be good, but it can also lead to some stress and anxiety. And Pete's point, whatever you do, it's better to kind of take a measured approach to your health in terms of all of the watching what you eat, watching your exercise, and doing all the smart things that we kind of are being told.

paul_roach:

Yeah, I think that's an outstanding summary. Outstanding, perfect. You know, I mean, I don't want people walking around being terrified, like, oh my God, I'm gonna get this cancer, I'm gonna get that cancer all the time. Like I always say to my patients, worry just enough to show up, you know? But worry enough to take good care of yourself. You know, that's the best that any of us can do. And if you do have access to a decent physician, take advantage of that. Don't ignore the person and

michael:

or be

paul_roach:

go

michael:

embarrassed.

paul_roach:

and... or be embarrassed, get your checkups, be honest, ask your questions. I always encourage people to write your questions down on a piece of paper before you go so that you don't forget once you're there. And you're very, you hand that piece of paper in right at front and you get all your questions answered. It's a great way to go.

peter_schlegel:

I was really dying during this evaluation or this discussion to regard, let me start over here. You'll probably throw this out in the editing room, but

paul_roach:

Oh, no, we'll keep

michael:

Never

paul_roach:

it.

michael:

keep

paul_roach:

We'll

michael:

that,

paul_roach:

keep it.

michael:

that's

paul_roach:

This

michael:

gold.

paul_roach:

is this is

peter_schlegel:

it's dripping

paul_roach:

real.

peter_schlegel:

michael:

Is there kind of the whole point of this whole, what is cancer is that we've, you've, you guys, you cancer types, you have figured out that what cancer is better than we understood before. And so you're now able to target it better than we ever had before. Like you're

paul_roach:

Yeah.

michael:

now, I think everybody knew it was cell growth out of control, but you now have, which is beyond the scope of this conversation, like we're still there, But the research is much further in and it's into the genetic code and they can say this is exactly what's happening and they can start to target it as Pete was just giving an example of a specifically targeted genetic deformity.

paul_roach:

I'm going to go ahead and turn Yeah, it's amazing. former vice president Al Gore And in that is a good book. I do recommend it. But in it, he mentioned that simple systems fail in simple ways and complicated systems fail in complicated ways. And it's extremely true. Like let's say you're talking about a baseball bat, how can it fail? Well, if I'm swinging it, it's because it misses the

peter_schlegel:

Ha

paul_roach:

ball,

peter_schlegel:

ha ha.

paul_roach:

but in other people, it cracks. You know what I mean? There's not a lot else that the thing can do wrong, but a complicated system has a thousand ways it could fail. So part of the reason we're talking about the cell itself and, and development and the 37 trillion cells he got and whatnot is your body is the most complicated system in the solar system. And God only knows, I mean, we don't know anything beyond our solar system, but it's exquisitely intricate. And even for Pete and I. You know, we're scratching the surface in terms of what we understand about cellular biology, compared to, let's say, a PhD who's been working on it, you know, on one little aspect of it or a group of them. It gets more and more complicated. And you're exactly right. The more we understand about normal cellular biology, the more we understand about where it goes wrong. And with cancer at every possible step, things can go wrong and be the source for cancer. There's never gonna be like one single cure for cancer because it's not a disease, it's a thousand diseases or more than that. So we have to take it one disease at a time. And so like for CML, Imatinib works really well. And if that stops working, then you give Synitinib. And if that stops working, then Arilatinib or whatever. That also happens to work for another disease that I deal with called a GIST, a gastrointestinal stromal tumor, which prior to those medicines was really impossible to cure. But now you can keep this thing at bay for many years because of those medicines with the same operation. So I think that's a really important thing. One thing I wanted to mention with... respect to summarizing is that, you're like wondering, all right, what's so bad about a cancer cell? What does it do wrong? How do you die from a cancer? And I don't have a short answer for that, which is bad, because I don't want to go running off at the mouth, but a cancer cell will do, let's say seven or eight really bad things. One, all your normal cells listen to the world around them in terms of should I grow, should I stay as I am, should I use nutrients, should I not. Cancer cells do not. They don't pay any attention to the other signals. They just keep growing and they grow and they grow even when they shouldn't. There are anti-growth signals, so it's sort of like a two-fold thing. It's like the brake pedal's broken and the gas pedal's pressed down. So not only are they growing more than they should, they are insensitive to the signals that they receive from your body that say stop growing. So they proliferate, and where there should only be 10 cells, there's a million. And they use up energy and they don't... do the original job and they cause. holes in organs and they cause things to block up and everything. Your cells have a program where if something's going wrong they will automatically shut down. Cancer cells turn that off. So they're completely on their own program. And your other thing is your cells are limited in the number of times that they will replicate. Cancer cells won't, they'll just keep going forever. And they're their errors will get propagated and become worse and worse and worse. Cancer cells will invade locally, whereas normal cells obey and respect their normal boundaries. And cancer cells will invade distantly. You think, all right, let's say a person has a breast cancer. Okay, well, we'll remove that part of the breast or the whole breast, and then the problem's over. It's not over because those cells got in the circulation. and they circulated and they landed in the liver or the bones or the lung or the brain. And then they're starting it all over there. And it multiplies. So you have one breast cancer that could turn into 50 or 100 metastases somewhere else. I could go on, they draw in their own blood supply, they have a number of tricks that they use to evade immune. recognition, and there's a few other things that they do. But that's what cancers do that are so bad. And that's why when those things get rolling, it causes huge problems for the person in whom it's happening.

michael:

I have a weird question now which you can edit out if you like. But here's my weird question. A long time ago I saw something about someone had a tumor growing in their body that had hair and teeth in

paul_roach:

Ah!

michael:

that tumor. Now is that cancer? Or not? Probably not, right? Because it's actually growing hair and teeth and that's a controlled thing.

peter_schlegel:

Yeah.

michael:

So it's

paul_roach:

It's

michael:

a...

paul_roach:

a

peter_schlegel:

Well,

paul_roach:

teratoma.

peter_schlegel:

we call that a germ cell tumor. Specifically, it's called a teratoma. And yes, it's pretty weird. And is it malignant in some cases, i.e. has invasive projections? Does it destroy the tissue around it and have the ability to metastasize? Sometimes. And sometimes they don't. Sometimes they can be. benign and not have that characteristic and then just keep on growing and growing. All of a sudden after six months or six years, it can change and they can become malignant and do those bad things in terms of doing what a dandelion can do.

michael:

Okay, so basically.

paul_roach:

And it is part of that, remember we were talking about that one cell becomes the entire body, and it's the germ cell tumor is, the germ cell is uniquely disposed toward doing that, toward becoming all kinds of different tissue types. And so that's how it happens.

michael:

Okay, and then within that, which is already a little bit skewed, it's already got a genetic instruction that's doing something it's not supposed to be doing. And then to Pete's point, it could be fine, but then within that system, a breakdown, further breakdown, could cause just a whole regular cancer in the rest of your body that could otherwise hit.

paul_roach:

Yeah, once it may progress further and develop very aggressive features that...

michael:

But that's not really different from the fact that that can happen anywhere else in your body It sounds like to me the really two separate things except that it's already a damaged cell Which as you guys pointed out? Makes it sort of predisposed to having more damage

paul_roach:

Yeah. If you need, let's say, let's just throw this number out there. An imaginary number of, let's say you need 20, um, genetic abnormalities before something's uncontrolled

michael:

becomes cancerous.

paul_roach:

growth and invasion and metastasizing, you know, maybe this one had 10 and now that's not, those aren't numbers you can take to the bank. They're just there for

michael:

example.

paul_roach:

illustration. Yes.

michael:

All right, well the other term that just popped up is benign versus cancerous. So aren't we talking about the same breakdown in mechanical structure and you get a tumor, which is also problematic from a genetic standpoint. It's also the breakdown of the cell machinery. What's the difference? Why is one benign and one's cancerous?

peter_schlegel:

I can try to answer that. I would suspect that the benign tumor continues to proliferate, but just as a big blob. And when it becomes malignant, then some of those characteristics in terms of invasive fingers or the ability to metastasize and spread elsewhere is gained. That would be my simplified version of benign versus malignant. And sometimes it's hard to differentiate the two. We have a term called in situ. A lot of these cancers are kind of like a stage zero. They're not invasive, but they will be. And the question is, you know, two weeks, two years, we don't.

paul_roach:

Yeah, there's a fair few of those things, whether you're talking a cyst in the pancreas or a tumor deep in your body, a lipoma that's deep in your belly that might grow someday into a liposarcoma, become a horrible actor if left in place long enough. The other thing is there are rare circumstances where benign tumors are really problematic. For example, if you've got a benign tumor in your brain, because it's your brain, that can still be a big problem. Obviously a malignant tumor is an even bigger problem, but there's that. And I think glioblastoma is a problem where it can begin as a benign, correct me if I'm wrong, Pete, but sooner or later it tends to become malignant if left long enough.

peter_schlegel:

Correct, it can de-differentiate, become more chaotic. And one of the very interesting things about brain tumors is that they do not metastasize their natural history, their behavior is such that they just grow with these tentacles, these projections, these fingers. And what makes the neurosurgeon's job so difficult and in fact impossible is that they need to resect out all the cancer, but leave the... the normal brain behind and that's the impossible task. That in the majority of brain tumors, the aggressive ones we call glioblastoma and anaplastic estrocytomas, there's really no way to detect just these minutely small amounts of cancer projections that are left behind.

michael:

that because of the brain blood barrier that

peter_schlegel:

Well,

michael:

it won't break out?

peter_schlegel:

that's why we don't do a great job with our systemic therapies, our chemotherapy, immunotherapy, and whatnot. But the main idea from those projections is you just can't resect them. I mean, some of the models of these brain cancers are that they project three, five centimeters or two inches from where we think they end based upon these very sophisticated scans like an MRI scan. And five centimeters in your brain is a huge amount of growth. And we had talked a little bit about a colon cancer. Yeah, if it moves five centimeters, well, you take five centimeters of colon out, who really cares? But even a couple millimeters of your brain can make a huge difference in your personality and very important brain function.

paul_roach:

All right, well, I think we should probably summarize. It's been about an hour and a half or so,

michael:

boys.

paul_roach:

and yeah, time flies

peter_schlegel:

Where did the time go?

paul_roach:

when you're talking about cancer. So I guess what I would like to summarize with is, well, first of all, Mike, do you have any questions that we have left?

michael:

No, I badgered you guys pretty well tonight, I think, and you did an admirable job of

paul_roach:

We

michael:

putting all my

paul_roach:

tried.

michael:

fears to rest.

paul_roach:

Pete, any saved rounds?

peter_schlegel:

I'm exhausted. I'm spent.

paul_roach:

All right, well, I am too, but I will go to the summary, which is in my mind that normal cell growth and development is in and of itself mind blowing to consider. And I think it's really important to think about normal cell growth and development when you're thinking about cancer, because it's just a, it's a distortion of not normal cell growth. And then point two is that abnormal deviates from this. And the usual cause is genetic abnormalities. People always say cancer is a genetic disease, which is the DNA, that's the instruction at the center of every cell that defines how the cell should behave. It's the thing that gets passed down from cell to cell and from one generation to the next. And there are multiple pathways and multiple genes that can go wrong. and in fact do go wrong for any given cancer. And as this happens, that cell will acquire aggressive, antisocial behaviors and will proliferate and proliferate and proliferate and invade and it will invade locally and distantly and create cell lines that progressively get worse and sooner or later compromise organ systems and the whole, the whole. organism. So in a nutshell, best as we can, that's how I think we could describe what is cancer.

peter_schlegel:

Excellent summary, Dr. Roach.

paul_roach:

We'll try, we'll try. All right everybody, we'll call it a wrap and I wanna say thank you again for dialing in, for tuning in to Sew It's Cancer. And please, any questions, write them to the website we have for this is something I set up. So it's letters at paulbryanroach.com, P-A-U-L-B-R-Y-A-N-R-O-A-C-H.com. Please write us with your questions and subjects and recommendations and we'll take them on. And special shout out to our fans in Mali in West Africa. You guys are the farthest away from here that are dialing in. So keep dialing in. We appreciate everybody. All right, signing off.

michael:

Good night.

peter_schlegel:

Good night.