 Thank you all for coming and Let's see if I can get organized here cancer is something that's a challenge for Everyone in this room. I'm sure all of you know someone or I've had an experience with cancer yourself or with relatives friends co-workers and It's why it's such a challenge is a challenge in itself So we're gonna talk and think today. I want to have a conversation with you about Why cancer is so hard to treat? What is it about cancer specifically that really See Challenges medicine challenges people challenges the field of nutrition exercise lifestyle everything is It's kind of stymied by cancer So let's start with some cases you all know of this gentleman when he was 25 he was diagnosed with Metastatic cancer and it was a serious situation. He had testicular cancer that had spread to the brain to the lungs and he survived and He received the usual standard treatment and That's given as a maximum tolerated dose Meaning that chemotherapy is given in amounts high enough to just barely not kill the patient But hopefully kill all of the cancer cells so that the cancer is gone and the patient's still with us. That's the goal Surgery is often unnecessary in Testicular cancer except for removal of the affected testicle But the metastases do not need to be removed surgically and in his case that was successful So what was it about his cancer? There was something about his cancer in particular That was amenable to this approach not all cancers are amenable to this approach and we'll talk about that in a minute so pediatric cancers cancers of Reproductive cells so the placenta the ovary the ova themselves the sperm themselves These are germ cell tumors or that the cells that make these to make these cells Coriocarcinoma is a disease of pregnancy And a problem with either the pregnancy itself or the placenta Certain types of immune cells can become cancerous and those are often easy to treat Relatively easy to treat and cure with chemotherapy lymphomas same idea tumors of The mature adult the tumors that you're all familiar with colon cancer breast cancer prostate cancer lung cancer those are a different animal and I use the word animal on purpose. We're going to talk a little bit about the evolution of cancer both in the entire Geobiologic time frame and within a single person But the tumors of early adulthood can't be cured unless they can be removed surgically and or treated very carefully and vigorously with chemotherapy and possibly some combination of chemotherapy surgery and radiation and that's only if they're in the earliest stages So that's a problem because 40% of cancer patients don't have one of these curable cancers like Lance Armstrong did They have something in this list and So metastatic carcinomas that includes the common ones that you've heard of breast pancreatic lung prostate colon sarcomas Melanomas chronic leukemias even though those are immune cells forming the tumor because they're slow-growing they're Paradoxically not curable same for chronic lymphomas. So let's take another case This is a 62-year-old man with prostate cancer and a PSA that's off the charts My laboratory at my hospital can only read PSA is up to 1500 So if your PSA is more than that it just says more than 1500. This is his bone scan You can see all those black spots. Those are metastases involving the bone so there are prostate cells in his bones trying to make Spermatic fluid those kinds of things. That's what prostate cells do, but they don't belong in the bone They belong in the prostate. So this man is sick. So we treat him with maximum dosage of the treatments that we have for prostate cancer and We treat him constantly and we treat him with as big a doses as we can In prostate cancer the current treatment the treatment is your is called androgen deprivation therapy andordans Of course being male hormones. So we deprive the prostate cancer cells of male hormones in various ways and the Patient gets better The PSA is too the scan looks much much better The relatives are ecstatic. Hey the treatment's working and The patient is usually a little more guarded like hmm. Wow is this see, you know, can this really be true? This sounds a little too good to be true, but they're they're they're happy But what happens what always happens what happens every single time? The treatment stops working Why is this? It's not just prostate cancer. This is a patient with metastatic breast cancer All of those black spots are tumors from the breast that have spread to other parts of her body and if she's treated with the maximum tolerated dose of The anti breast cancer drugs which are different than the antipros to cancer drugs She will get better for a while and the scans will look better for a while Then the disease will come back or it was never gone, but it will roar back look like this again and the patient will succumb so so why is that and The answer is partly contained. I think in our popular culture Who has seen the lion king? Okay, I am I'm gonna tell you all about this movie and I have to tell you first that I haven't seen it, okay So don't judge me. I will I hopefully I can go see it this weekend But I haven't seen the previous version either, but the lion king from the previews It's a and don't spoil it for me those of you who've seen it. Okay. No spoilers. It's a coming-of-age story and And The baby lion the lion cub has to become the lion the next lion king and how does he do that? He overcomes obstacles and it sounds like the obstacles are going to be pretty darn tough All right, so I think that's what the movie is going to be about and that is what cancer is about It's about overcoming obstacles cancer has a lot of obstacles to overcome before it can get a foothold in your body So your job and my job as the oncologist is to make sure that it Doesn't get a chance to overcome those obstacles the other thing though that I think is a little more subtle is Well the back of the movie, okay, I don't want this cancer is depressing. Let's talk about the movie for a second the lion king this Cub has to become he's not becoming the lion prince or the lion. I don't know you know Burger flipper, okay, he's becoming the lion king So that means he has to overcome kingly obstacles So Walt Disney or whoever's running this movie starting this movie is going to put big obstacles in front of him That's something that we are just starting to understand about cancer Maybe we don't want to put big obstacles in front of a cancer. We can't cure so I'll let you think about that for a second and Let's take a little detour down history And talk about why cancer even exists in our biosphere. Why is there cancer? What a horrible thing? so cancer is a result of evolution and evolution is about The only the strongest survive right? How many think only the strongest survive evolution? Oh, you guys are too smart. Okay, so Oopsie. Oh, well, you saw the punchline. Okay, so this guy is probably stronger than that camel But only in a certain context you put him in the desert This poor guy survived by the way This was a heat wave in a zoo in Argentina and they dumped ice on him for two weeks to the heat wave past And he made it but in any case you can see that he's not in any mood to reproduce here He's in the honey. I've got a headache tonight mood And nothing much is going to happen In the survival mode, so it's not survival of the strongest It's survival of the fittest and by fit. We're not talking about strength. We're talking about fit How well do you fit in your environment? How well does your environment fit you in? in terms of making it easy for you to reproduce so of course a camel has to be in the desert and a polar bear has to Be in the Arctic and that's where they reproduce best Switch places and nothing good is going to happen in terms of reproduction So evolution is about who gets to reproduce fitness is about who gets to reproduce Cancer is about who gets to reproduce on the cellular level So cancer has been around for a long time and I'm going to give you a hint cancer arose when single cellular organisms decided to band together and not be single anymore and form multicellular creatures Cancer is not a disease of modernity cancer has been Plaging all sorts of creatures long before pollution of the current modern type anyway an Egyptian mummy with breast cancer has been found and Not to pick on the Egyptians. This is the mummy. This is the remains of a hip bone from someone in Siberia with metastatic cancer Thousands of years ago So if cancer is one of the trade-offs for being a multicellular creature Why would that even happen? Well Because being multicellular Increases your ability to reproduce So if you're a single-celled spheroid creature If you become really large your surface area doesn't go up proportionally and your surface area is how you take in food So if you're a single-celled creature, you have to Soak food in through your through your cell Wall or membrane and there's less of it proportionally the larger you get But if you have lots and lots of different cells The surface area can be maintained and indeed in your intestines, you know I forget how big it is, but it's something like several tennis courts if we actually flattened out the surface area So you can take in a lot of food and as the previous speaker pointed out that's both good and bad Multicellular creatures can live longer because they have a division of labor so we can Live a long time many decades a protozoan or a single-celled creature might just live a few minutes Maybe a few days, but they're in a sense immortal in that when they divide There are two of them. There's no death with that and let me let me let you think think about that for a minute, too so a Single-celled organism has to have an awfully good reason to agree to align itself with other single cells and Live that way So alignment of fitness is what evolutionists call this and it occurs at the moment of Fertilization so when the sperm fertilizes the egg and the zygote is formed at that moment The fertilized egg at that one moment You've all been there. You were just one cell That only lasted for maybe less than an hour before you divided and we came to and we were on our way to multicellularity or you were But in that moment you were aligned With one goal the goal of that zygote and I'm talking biologically. I'm not talking philosophically or Spiritually or anything like that, but the goal of that zygote is to mature and get its DNA to the next generation. That's it All of the rest is expendable Okay, so that DNA Has to be present in every single cell in that multicellular organism that way they're all aligned We all have the same DNA. We all want to get that DNA to the next generation To once they're aligned then they can agree to adhere they have to stick together You don't have part of you here and part of you over there You're all stuck together These cells have to communicate they have to cooperate And they have to specialize you can't all do the same thing I mean, I guess there was that movie the blob where the thing rolled around and everybody did the same thing in that in that giant massive cells, but for you you have different parts and The goal again is the Transfer of the genetic material to the next generation and that is called the export of fitness So there's a terrible price To be paid for being a multicellular creature and that is That Almost all of you. I don't mean all of I can't pick on you. I'm gonna pick on you right here. Okay Almost all of you is going to die, but if you have kids a Couple of you know one or two sperm or three or four. I don't have any kids. Yeah, okay So so two sperm are going into the next generation. Bye-bye. They're they're off. You've exported your fitness But the rest of you not so lucky the rest of you has made a pact with those sperm cells in your case That we will die and we will support you with all we've got until we die so that you can export Our genetic material to the next generation. It's a pretty heavy packed So It's kind of interesting When you do something like that you're kind of putting All your eggs in one basket literally the ovary all right and And then you watch that basket So the purpose of a multicellular creature is to carry its genetic materials sperm or egg to the next generation and be really Careful until that happens after that's done. There's no evolutionary pressure to prevent death That's why cancer occurs mostly in older people. You can't select for something that happens after You can't select evolutionarily or fitness wise for something that happens after reproduction So we talked about how multicellular organisms are Composive cells that have to cooperate In the for the one single purpose of advancing the genetic material to the next generation well You were once a single cell That single cell and all of your cells that are descended from that have a memory in them of their days swimming in the Paleozoic ocean. I'm sure I'm getting the geologic age wrong but In ancient seas as single-celled Freewheeling organisms that didn't have to worry about anybody else they remember that all those genes are still in there They're layered on top of on top of those are layered new genes that make you human but those old genes Can be covered up and one way to think about this is that they can also be uncovered and Make it back into the world and that happens with aging there are fences or barriers to access to those old programs but Those can be worn away with age. So that's one way to think about that and the reversion to Individualistic behavior lack of cooperation loss of cooperation can result in one of two things Cell suicide there are suicide programs that will kill a cell cell will kill itself if it's starting to Wobble in its commitment to the entire organism The other thing is if that suicide program is also damaged Cancer can form So loses its ability to cooperate with the rest of the organism it goes for itself It likes to divide because that's what single-celled organisms do And you have a cancer so again larger body size gives you an Larger number of cells in which this can happen. So there's just a stochastic or statistical risk with being large There's also a risk as the previous speaker pointed out with bigger body size within a species. So And that's mediated by things like IGF one If you have a large animal in a species and a small animal in a species The larger one will be at greater risk for cancer and that includes humans So a good example is great Danes very high risk of cancer most of them have cancer by the time They're five six seven years of age and they die of it Whereas Chihuahuas can live to be 17 or 18 they do get cancer But they get it much later and they don't get it as much as great Danes do and that's because great Danes and large dogs in general Have more IGF activity. They may not have actually more IGF, but they have more IGF activity That increases the risk of cancer And of course the longer you live The greater the risk of cancer. So cancer is seen again in all all sorts of creatures. They're multicellular This is a hydra on the right is an abnormal hydra with a funny bump on its side. It's got a tumor Mushrooms fungi if they're multicellular can Develop tumors even though we use them to treat cancer they can develop cancer themselves This is a mushroom with a tumor and you can see it's a fairly well developed tumor There's a it's trying to grow a second cap Up on top there. You can see the gills in the in the tumor and here's a cactus a saguaro cactus with a tumor on top So let's talk about cancer Developing in one organism. We've just kind of taken a look at cancer in the entire Biosphere, let's look at it inside one creature. So a cancer needs an ecosystem if You have a cancer you are the cancer's ecosystem. So you want to make your ecosystem very inhospitable So dinosaurs like warm climates when the KT event occurred And the asteroid hit the earth a lot of the dinosaurs were killed by the blast and the Tsunamis and those kinds of things but most of them died out over the next many many thousands of years from Type of nuclear winter if you will a big cloud cover that cooled the earth and made it very cold and dinosaurs didn't do Well mammals which were warm-blooded then became ascendant because they could regulate their temperature The guinea head was a fowl in North America that went extinct from many small insults It was hunted there was a big blast of hunting because they were I don't know I guess they were there Maybe they were good to eat. I don't know and then there was a little guinea-hen conservation effort in the northeast and some farm had something like several thousand guinea-hens and Then there was a guinea-hen flu a lot of the birds died of some epidemic in this farm And then they had a few left they had something like 200 left Kept those around for a while and tried to rehabilitate the population But the barn burned down and that was the end of the guinea pigs. So there was this big bang, you know, everybody hunting them lowering the population and then the population became Unstable and vulnerable because there weren't quite enough to sustain it and so further insults such as the guinea-hen flu And then the barn burning finished off the species The bull weevil is a pest of cotton crops Which destroyed much of the economic value of the southern cotton crop in the United States in the early part of the 1900s We'll talk a little bit more about that in a minute and then cancer is A condition that takes place in an ecosystem, which is an individual an individual organism So what are ecosystems provide for cancers and for every everything else that lives in an ecosystem? They provide all the things that you need To be able to mature and then ultimately reproduce which is again is the goal And they also contain some challenges so Let's look at the the cancer Ecosystem in the human body. So a cancer needs fuel and cancers can use Fats and proteins and nucleic acids and other things as well as glucose many cancers prefer glucose But it does not mean that they can't use these other fuels So when you use the ketogenic diet, you want to combine it with some other treatment that combines insults sort of in the guinea-hen extinction paradigm Just doing something by itself is unlikely to be With food is unlikely to be completely successful space a Cancer does better in a kind of an open space in many Many times in a relaxed tissue a cancer can have predators Okay, the immune system the oncologist coming to get it getcha Okay, it needs transportation needs to supply chain for its nutrients and it needs waste removal Climate in a sense that's a bit of a stretch, but pH toxins You know heat and cold all of those things can affect the growth of a cancer And they're different in different parts of the body So you've noticed that certain cancers you may have noticed that certain cancers have a propensity to grow in certain organs So for instance hormone receptor positive breast cancer tends to grow in the bones Well, it has it likes calcium milk is made out of calcium. These are cells that are trying to make milk So they go where the calcium is Colon cancers like to spread to the liver the liver is kind of a nice place. It's directly in the transport line It's the next bus stop in terms of blood flow from the intestines to the liver there's just one stop there through the portal veins and The liver is full of glycogen and also fat in many cases and there's a lot of food there a lot of blood flow And you get the picture so and then there are competitors in an ecosystem so again fitness is about fit so a cancer has to fit into its ecosystem and In the early phases of a cancer a cancer is often not extremely aggressive More like a farmer and I don't mean this in a good way like a farmer is a person who you know produces food and value for You know community. This is not what we're talking about. I'm just talking about how a cancer Situates itself where it finds itself and how it makes use of the resources that it has access to so Farmers are really good human farmers are really good at adapting the landscape to fit their needs they can Create irrigation. They can rotate crops. They can till the soil if necessary all sorts of things and As long as a farmer is able to do these things the farmer is going to do what they do Which is farm same with cancer cells? So a cancer might be there how dangerous is it in the earliest stages? Well, this is something that we're just starting to think about in some new ways Should we get all excited and I don't know cut off its blood supply That may not be an appropriate response what happens when you cut off blood supply Then the farmers may start to starve if you cut off their irrigation system the crops don't grow they can't eat They may become unhappy. They will respond So all living creatures including cancer cells respond to perturbations in their environment and they try to maintain or Return to a kind of homeostatic mechanism So They will change themselves to fit the environment or they will change the environment if they can't do that they'll leave That's called metastasis and cancer. We don't want that If we dump a lot of chemo on this early cancer that might happen they might leave They also can produce a lot of acid and invade the neighbors Just move in next door. Of course, that's not good for the neighbors They might get on the highway and drive to a different organ and take up there But if you perturb a cancer too much you will make it more aggressive and that's what we saw in our first two cases so the bull weevil after World War two the bull weevil was treated with DDT and From 1950 to 1958 that worked and then it stopped working. Does that sound familiar? and now Ecologists and oncologists are starting to talk to each other because we're both dealing with the same problem, which is pest management so again an organism responds to perturbations in its environment by doing something What you don't want a cancer to do is get worse and leave so How can we do pest management in human cancer? This is a prostate that's been sectioned the yellow part on the right side of the screen is the tumor This is the metastasis. We've seen this fellow The purple cells are treatment sensitive. This is a tumor. Okay There's one treatment resistant cell in this tumor if we remove all the treatment sensitive cells The patient scans look better, but what have we really gotten? we have Tumor that now is smaller, but you see that there's more green or resistant cells Does that make sense? What happens if we keep doing that? Well, basically to make a long story short We end up with all green cells the whole situation is worse than at the beginning and the patient is going to die And that's what always happens with androgen deprivation therapy for metastatic prostate cancer always So why do we do that? We make cancers resistant well, we're not doing that anymore. We're we're trying to get away from that but What are there other things that we could do other treatment paradigms and the answer is yes Somebody's holding up a five-minute sign. So I better get on with it here We can give a lower dose and we can give the doses less frequently and then what happens is that you see here We have fewer purple cells There's only one green cell here oopsie And then we we don't treat again, you notice in the second arrow going to the right There's a no treatment over it We let the purple cells recover Anyway, you get the idea here. We try to give as little treatment as we can so that we can keep treating Does this work in real life? It's a nice idea. It does Two cohorts of men with prostate cancer 11 patients received this type of treatment called adaptive therapy low dose intermittent and 16 patients received the usual standard constant therapy to make a long story short 10 of the 11 patients in the experimental group Did well and we're still Stable at 24 months Whereas 14 of the 16 patients were worse at 14 months and Not only that much less drug meaning fewer side effects was the result For the patients who did better So how about the patient with metastatic breast cancer? So I'm going to tell you about a case report of a patient with triple negative the worst kind of breast cancer hard to treat Metastases to lung liver and bone not an early stage 15 years later at 72. She's alive and well has a good quality of life. She's off treatment. It has no signs of this cancer How did this happen? They gave her a big blast of treatment up front and then they followed it with an entire year of weekly treatments and they rotated the treatments over Every two to three months so she was never kept on the same treatment more than two or three months In other words, they didn't wait until the tumor got worse on the scans to change the treatment So I call this extinction therapy. This is kind of the KT event for a cancer You blast the heck out of it at the very beginning and then you keep the pressure on with a nuclear winter over the next few years so when And these are the details if anybody wants those you can have the slides afterwards, but let me just summarize here So there are three ways to treat cancer You can apply curative therapy But you'd better make sure that you have a type of cancer that will respond to curative therapy by being cured If you give a maximum tolerated dose of cancer therapy to a cancer that can't be cured You may make things worse These are the cancers that can be approached with maximum tolerated dose and should be pediatric cancers cancers that arise in the reproductive cells certain immune cell cancers and Then curative therapy can be applied usually with surgery and radiation and also a combination of chemotherapy or any any combination of those In early stage cancers of maturity Extinction therapy this is for those cancers that you think you might be able to cure That usually aren't cured if you were going to try to cure them How would you do it you blast them up front and then keep the pressure on constantly for at least a year? At least that's what worked in that case that I showed you and then there's adaptive therapy Which means you coexist with cancer you give up trying to cure the cancer Does that mean you just don't treat it? No, I mean this picture is supposed to be kind of silly. Okay? That's not really realistic you keep the Tumor sensitive to treatment by treating it very very gently you try not to turn it into a marauder So you use the lowest necessary dose you dose very infrequently and You do that based on the tumor growth not a calendar or an oncologist's schedule or guess and the goal is to weaken the nasty parts of the tumor And strengthen the host's ability to resist that tumor and Thank you very much. If you have any questions, I'll take this So we have about five minutes for questions of someone that come up and ask a question We have five minutes for the questions. So I I've heard an idea about You know prophylactically trying to minimize the risk for cancer of Fasting, you know for extended periods of time with the idea that it can you know kill off cancer cells And so what as you're giving her talk it occurred to me that with that strategy possibly perturbed You know perturbed something that's has the potential to grow and actually have the opposite effect potentially So we do see that sometimes in advanced cancer. So we see People doing a lot of fasting eventually the cancer itself may become resistant to fasting because again Cancer does respond to its environment, but animal studies are very very clear To fast before a cancer appears appears to be very very salutary It appears to be one of the very few things that can actually not prevent cancer, but delay its onset So you still I think I really want to say this I want this to be understood Fasting does not prevent cancer. It delays it That's good because hopefully you will die of you know something else at 120 before you ever get cancer But fasting is effective in delaying the diseases of aging including cancer. Yes Fantastic talk I really love your work dawn Could you give us an idea as to why there's this prevailing misconception? around a ketogenic dietary approach and sugar and carbohydrates being the only Villain in the root cause of cancer and cancer proliferation What do you thought on that when the evidence obviously suggests that isn't certainly isn't the case So I think that you know, that's a really great question And the reason is is that some of the early work with ketogenic diet any dietary perturbation is going to be effective in the beginning so when you Do something to perturb the landscape for the farmers It's going to be very effective. It doesn't matter whether you burn the crops or you cut off the irrigation or you introduce a pest You know or you send someone to steal all the produce but but The system will respond the farmers will figure out a way around each one of those problems And I think that's what we've you know, that's just what we're seeing we looked at things And saw this nice response and our hope was oh wow, you know, this is this is it But it turns out not to be it that it does give a clue. So if you Just do one of those things to the farm you steal the crops or burn burn the fields or cut off the water supply You're probably you know not going to permanently Remove that farmer from from business. They're going to respond But if you do all of those things or as many of those as you can all at once You have a much higher likelihood of getting rid of that farm and farmer So that's kind of the paradigm that I think right now we need to work with with cancer And that's to to come at it with several different approaches at once You don't want a serial approach, you know first I'm going to do this and then I'm going to cut off their water supply and then I'm going to burn You don't want to do it that way you want to Do it all at once. The other thing you want to do is make sure that when you are treating a cancer you Strategize so if you're if you decide, okay, I'm going to burn down this field. Well, you know, I'm going to do a couple of things Are you going to? Burn down the field and Then cut off the water supply no First you cut off the water supply Then you burn down the field Well, there are ways of sequencing cancer treatments that make the same sort of sense so that when you apply a second treatment The first treatment has already prepared the way and made it much more difficult for that cancer to recover from the second treatment that you're going to apply so I think that We as human beings tend to get really excited and we should about any inroads that we can make with cancer And I think that the work with ketogenic diet is fantastic I use the ketogenic diet a lot and I use fasting a lot with my cancer patients during treatment But I do caution them that that's not something that's probably going to work all by itself in the same way Just chemotherapies unlikely to work all by itself. You want to combine these things. So I hope that answers your question somewhat Thanks, son. Excellent as as usual my my question is kind of like a follow-on from Darrell's I think as me and him and some others in this room, we're probably approaching the great Danes of the human species So maybe we're we're we're a bit more worried about this and this there's certainly some talk about overall minimizing Total growth factors total like tour activation to try and minimize cancer growth and there's one about your your your thoughts on that because You know, we may want to think about balancing cancer versus our risk of Suckapena for you over breaking a hip and dying in hospital of pneumonia And so do you have any any any thoughts on how how those of us who are worried about that might think about that So there are all these trade-offs. So, you know more growth hormone you have for the bigger you are the more likely you are to reproduce Okay, women like large men apparently human women. Okay, and they would be more likely to choose you. So That's a trade-off There are also trade-offs at different parts of the lifespan So in old age having too low of an IGF one is a risk factor factor for death Because you get the sarcopenia osteoporosis the Parkinson's Alzheimer's those kinds of things You need the some growth hormones to keep things juicy and and strong in old age So there's very much a knife edge And I think that the way to do it in the way that I like to look at it and the way the way I try to do it When I'm not eating pound cake, which I did have some last night was delicious, but That's rare, but is to make sure that you are you know staying flexible in terms of your Metabolism and it's very important to be sure you can can walk both sides of that That you can deal with excess growth hormone if you have some at the moment after a nice workout and a good meal and that also you can't deal with the Famines that come along either on purpose with fasting or not and that you can prevent Alzheimer's and those kinds of things. So I think it's very it's a great question I don't have all the answers. No one does, but it's a you know something we should keep asking and thinking about. I love it So let's give her a big round of applause for a great talk