Three must-dos to cure cancer | Timothy Cripe | TEDxColumbus

Since I was little I've been curious about how things work now, most kids, when they get a new toy, they want to play with it, but I always wanted to take it apart, but you know, I think that might have made my parents angry, but I indicated to them that I wanted to become a scientist, which I did, but I also had an event happen to me in high school that made me want to become a childhood

cancer

doctor and that's when my good friend, the younger brother, was so young. child Steven Daniel Jeffries was diagnosed with

cancer

Steven died at the age of 8 in 1975 in Columbia Maryland where I grew up due to a rare type of pediatric cancer it was my first experience of what cancer can do to a person what cancer can to do to a family to a community and I have learned a lot since then.

I learned that it took me 17 years of training to become a physician-scientist and in the more than 20 years that I have been practicing and caring for patients, I have learned that there is actually reason for hope there is reason for hope because research

cure

s cancer, but it is We may have to rethink some of the things we've been looking at in terms of the development of others, let me explain, acute lymphoblastic leukemia or all are the most common. type of cancer in children and this graph shows the survival or percentage of life of the patients according to their years since diagnosis and in the year I was Stevens, 8 years old, 1968, the survival of the patients was still quite bad , so 50% of the patients who can be seen on the dotted line only made it to two years and only 10% of the patients made it to six years or more, but through careful application of the research that is testing hypotheses, this might work better than what we are doing, rejecting things that didn't. didn't work and by leveraging the things that did work, we were able to double that long-term survival when I was 12 and we as a medical community continued to work on that and by the time I turned 17, the patients diagnosed that year had a remarkable

cure

rate of 60 percent, we did not stop there, however, over the next years and decades we continued to try new things as a community as scientists and medical specialists until the year I turned 49, when ninety percent of the patients were cured, that's the most recent one. year for which we have dated data because we have to follow it for five to ten years, so we believe that today if you are diagnosed with standard risk acute lymphoblastic leukemia in children in childhood, you have more than 95 percent survival, That's surprising, so my lesson is to trust.

In research we rely on science not only to find out how things work, which I love doing, but also to make the world a better place to save lives, but cancer is still the most common cause of death between the two and children, so we

must

have a little more work to do, what do we do with patients with advanced cancer? Like a cake. An 11 year old girl who came to see me with this PET scan. You can see the outline of the image of her and all the dark spots on her, except her bladder, which picks up the marker. all the other places are where she spread her tumor.

She had a metastatic sarcoma. This result for patients with metastatic solid tumors or other types of leukemias such as acute myelogenous leukemia remains like everything in the 1960s again, survival was based on years of diagnosis and the survival of all patients with advanced cancer falls into somewhere in this shady range in 2017, why haven't we done better? I present to you that the strategy we have been using to develop drugs is somewhat flawed, so to determine how to do it better we have to go back to biology how cancer works so we all know that you probably learned in your high school biology class that the cell divides and those two cells divide more and more until a massive cancer arises.

It is usually a clonal population of similar cells and at some point one of those cells breaks and goes down the blood vessel or a lymphatic channel and finds another organ like the liver longer and it starts to divide there, which forms the metastasis as we saw in Kate and what we have done in the last few decades is take some of these tumor cells and grow them in a dish or put them in a mouse and test drugs in the mouse dish and then use only those that work in the dish or in a mouse and test them in people, but we may be missing a lot with that simplistic view of the world;

We actually know a lot more about cancer than that, so I did a keyword search for the word cancer in the world's medical literature and discovered that I have published over 3.5 million posts about cancer and this year alone there have been added more than 135,000, so now we know a lot. I haven't read them all, but I have tried to look through the literature to find out what some of them are. the key features we need to look at that might explain why we haven't cured some of these other cancers. I narrowed them down to

three

key characteristics and the first one is illustrated in this diagram, so it comes from a post by Lee. ding and then Elaine Mardis Rick Wilson and both at Nationwide Children's Hospital in Columbus Ohio and 36 others published a few years ago and were able to genetically trace single cells in this case in a nice patient with myelogenous leukemia.

You can see those cells on the left. and they are used to track how those cells fared over time and you can see in this particular patient that the gray cells expanded to become the main dominant population in that person and then over time other cells appeared. cells, the orange, the rose, and with chemotherapy that composition. changed, most of those cells were gone, but some of them remained and then expanded even more, so later in relapse most of the cells are orange or pink with some gray. Now these are different cells that acquire mutations, either genetically or epigenetically, which means changes in the gene. expression, so I like to think that your hardware or software has been corrupted from a normal cell, which gives diversity or heterogeneity within the tumors, so you don't have all that white, all those white blood cells like you saw before the second thing. is that tumors are not just made up of tumor cells, they actually have many normal cells, cancer associates with normal cells, they recruit them into their microenvironment and coax them into doing things for them.

Normal cells produce substances that help tumors grow. help them resist therapy this is a microscope image of a tumor in my research lab where we could say stain the cells, you can see all the blue cancer cells and then there are brown cells and pink cells, those are T cells of different types may be there suppressing immunity or they may be there trying to fight cancer because T cells are part of the immune system. We also know that there are many other cells that are normal cells in 200 macrophages, other myeloid cells. fibroblasts that help feed the tumor, so when we put a cell in the dish and culture it, those are not there and the third thing was an experiment that blew me away when I saw it and it was done by Juan Masa Gay in New York.

A few years ago he dyed one tumor green and one tumor red and implanted them on different sides of the mouse and after a few days removed them. Zoomers looked at it under the microscope and each one of them was a mixture of green and red, so different sites of the tumors are collaborating, they are communicating, if one of those cells corrupted by diversity manages to figure out how to make a tumor better, can transmit that information to all the other sites, in modern words we would probably call this collusion, which gives us a different strategy a different picture of cancer that I'm not just for you now instead of just two cells that are the same we know that Every time a cell divides they are slightly different they acquire some corruption in their software or hardware They evolve, change and continue to do so as they divide and divide, so you get a heterogeneous mass of which some cells are made.

I respond to your treatment, but others may not, and we know this when these cells break off and move down their blood vessels. as we saw before and they go to a different organ, those cells begin to divide in that other organ and in that metastatic site they are evolving, they are changing, so what is in that metastatic site is different from what is in that primary site and probably different from all the other metastatic sites and when we take one of those cells and put it in a dish and culture it, it continues to evolve, now it's adapting to growth in a dish, so it changes, it's no longer the same as was not that person if we put it in a mouse, the same thing is different, so when we test drugs in the mouse dish without the presence of normal cells without the collusion between different sites where we could be fooling ourselves and missing many of these tumor cells when This difference should be recognized by the immune system, which are these blue cells, these T cells that come from the vasculature and that normally kill or destroy infected tissue or tissue that should not be there.

Strange fabric. That's what organ rejection is and they should reject it. the tumor and we see T cells on the slide like I showed you, but they are not doing anything, they are inert, they are just dormant, they are suppressed and now we know why we didn't understand it. This has been going on for many years, but in many cases it is those normal cells that enter the tumor and produce tgf-beta il-10 PDL substances. These are molecules that suppress the immune response and do not allow these T cells to reject the tumor so we have to think about that and finally the collusion that I talked about these tumor sites are exchanging information not only are they exchanging tumor cells those red cells and greens are exchanging some of these normal cells have been adapted or forced to do the bidding of the tumors, they are normally marketing those substances that suppress immunity and it is a big conspiracy against us.

Metastatic cancer is like an organism that lives inside us and conspires against us, so we

must

think about these

three

characteristics of cancer if we are going to make progress against advanced cancer the corruption of genetics diversity the coercion of normal cells that do not are present on a plate and collusion between sites that feed and help each other, so I challenge the medicine community, whether you are in the pharmaceutical industry, a cancer scientist, whether you are an advocate who is raising money from projects and supporting research, for which we appreciate you, ask yourself what am I doing or what am I supporting, addressing at least one, if not all three. of these characteristics of cancer because they are what will take us to the next level in curing advanced cancer, corruption, coercion and collusion, definitely something since CNN should be interested now in what we are doing in my research laboratory in the Nationwide Children's Hospital here.

In Columbus we are injecting these tumors with live viruses, the viruses are attenuated, which means they are crippled, they don't cause disease, they can still infect and kill some of those tumor cells and we are combining this and that, that tricks the cancer. Think about the immune system, think of cancer as an infection and bring in all those T cells and when we combine that with drugs that target some of those normal substances, those normal cells, we can lay the cancer bare and get some results. contraction are really good and we hope to achieve the same kinds of things in people, but there are probably many other ways that we as a scientific community can think about how to address those three Cs.

As you can imagine, it takes time, as you saw several decades , achieve real progress. Still, it takes money, so I thought I'd check with our National Priorities, since it was Halloween, we spent over eight billion dollars with Abby on Halloween candy, which is three billion more than the entire Institute budget. National Cancer. and the National Cancer Institute is the largest public funder of cancer research in the world. We spend about half that amount on hot dogs each year and eight billion dollars on Fourth of July fireworks, which is four times the amount the National Cancer Institute spends on children alone. 4% of the National Cancer Institute's budget goes to children.

I had the privilege of spending some time in Washington DC at a candlelight vigil about two months ago. It was quite a moving experience, not only were we paying tribute and remembering those we lost, but we were trying to raise awareness about cancer research and about funding, and these are peoplewho know the power of research because they are people who know everyone's history, through research we have been able to cure all cancers, let's not stop until we cure all cancer, thank you