Episode 47: Math Meets Cancer

Episode 47: Math Meets Cancer

Karie Dozer [00:00:05] I'm Karie Dozer, and this is TGen Talks. Cancer, although it is the second leading cause of death in the United States behind heart disease, nearly 40 percent of all Americans will be diagnosed with cancer at some point during their life. At TGen, researchers are not only using genomics to develop more personalized treatments for various types of cancer, but researching the origins of cancer in the body, trying to create better and more effective tests for cancer because earlier diagnoses mean better outcomes. On this episode of TGen Talks, we'll meet a new faculty member at Teach TGen, one whose dream is to develop that better test, a simple blood test to find cancer as soon as it starts. Dr. Christian Thomas, it's a pleasure to meet you … welcome to TGen by the way, and thanks for taking the time to talk.

Dr. Tomasetti [00:00:56] Of course. Thank you. Thank you for having me.

Karie Dozer [00:00:58] You are pretty new around here. Can you tell me a little bit about how long you've been with TGen and City of Hope and what it is that you do here? What's your title?

Dr. Tomasetti [00:01:07] Yes. So I've been here for two months and I'm the director of the Center for Cancer Prevention and Early Detection at City of Hope and professor and director of the Division of Integrative Cancer Genomics here at TGen, as well as professor and director of the Division of Mathematics for Cancer Evolution and Early Detection in the Department of Computation, Quantitative Medicine at the Beckman Research Institute at City of Hope.

Karie Dozer [00:01:33] You sound like you have a pretty long title and a lot to do. Where do you spend most of your time?

Dr. Tomasetti [00:01:38] Yes, so I spend a lot of time in both places. We are opening the center for essentially for cancer early detection and prevention. And the idea is that today, even with all the research that that's been performed in cancer research, unfortunately, the mortality is still very high. In fact, just to have a number since 1971, when Richard Nixon declared war on cancer, the decrease in mortality has been in cancer. Mortality has been 20 percent, which I personally find it disappointing. So I don't think we definitely have not won this war yet. And due to some research, I did with some colleagues in the last 10 years, we have discovered that a lot of cancer is not caused by environmental exposures or injury to factors. Now those are important. I'm not saying that they are not. We don't want to smoke. We don't want to expose ourselves to much of the Sun. But it turns out that there is a major fraction that actually is just part of the normal processes acting in our body cell division, really. And when the cell divides has to duplicate to make a copy of the DNA and when making a copy of cells, I'm not doing this perfectly. So there are a few mutations every time. And so it's like depending on luck and where these mutations hit our DNA, you may end up in the long term with cancer. And so having discovered how large this is, the role of this normal cell division processes, it became apparent that if we want to have an impact on cancer mortality, we need to find cancer very early. Because if cancer was caused by just by smoking, cell exposure, and so on, the recipe would be we prevent exposures that we are done. And this actually was the message until 2015 until this, these discoveries that we made and. But that is not the case. You know, there is, in a sense, a civil war inside of just our cells functioning normally. The idea is that you can discover tumors and cancer earlier than what is done today. And there is a lot of data out there showing that if you find cancer at an early stage local, then you essentially can with surgery, remove it and you're done with that. And in breast cancer, for example, more than 98 percent of the patient population after five years is alive. If the cancer was found like a stage that changes dramatically if the cancer is found in stage four or metastatic and all of that. So I think that that is really where we're going to make the most progress. And so a cancer center like City of Hope, I believe, should benefit from having a center that focuses on early detection of cancer.

Karie Dozer [00:04:57] Most people who know about TGen and about City of Hope think of both of these institutions as those that help to fight cancer once it's found, rather than prevent it or detect it. And your emphasis is, well, it's the other half of that equation.

Dr. Tomasetti [00:05:13] Yeah, and it's exactly this combination of generosity of hope. That's why I'm here to do cancer early detection. You need methodologies. And today what is very exciting is that we are really obtaining those methodologies. And the most typical right now, it's a blood test. It's a simple blood test, something that you can envision taking once a year at a doctor's office. And  the blood test has the ability to find essentially. Cancer across various, you know, all major cancer types you can think of and at an earlier stage than what you would do when you have symptoms. And this there are already there have been prospective studies showing that this is working. And so the idea is to continue building better and better methodologies. And TGen is an amazing place for building new technology. And, you know, it's a sequencing powerhouse and not just a sequencing powerhouse, but there are experts across the spectrum, you know, cancer biology all the way to, yeah, bioinformatics and the combination of TGen with the clinical, you know, outreach, the something like the seed of hope has represented a really perfect setting for this center.

Karie Dozer [00:06:43] In some ways, your resume is a little different than that of most of the researchers here at TGen in that your background is not in science or genetics or medicine. It's in math.

Dr. Tomasetti [00:06:55] Yes, math's been in my blood. It runs in the family and initially, I'm from Italy. You probably can tell I sense from my very thick accent. But so I guess in Italy, you know, the economy is not the American economy and we mathematics, you can't do really a lot of things. And so for practical purposes, initially, I actually went into math, applied to finance. But then pretty quickly I discovered that it wasn't providing me with what I thought for me was meaningful or particularly meaningful. And I always believed that mathematics has the power to really have an impact on our daily life. I mean, we have plenty of examples. And so during my Ph.D. here in the United States, I discovered this application that was cancer. And so understanding how cancer happens and all the way to detecting cancer. And so that's why a mathematician can be in a cancer center or a director of a center in a cancer center is because today cancer has become. Understanding cancer has become so sophisticated that it's not anymore something you just, you know, you cut tissue and you look at it. I mean, that's still very important. But thanks to sequencing it's now it's about sequences of billions of letters and this becomes, in a sense, mathematics. And so I love it.

Karie Dozer [00:08:31] You said you discovered something about how mathematics connected to cancer, this discovery of yours? What was that?

Dr. Tomasetti [00:08:36] Yeah, it was during my Ph.D., I was looking for a meaningful application and there was some work trying to understand why certain patients develop resistance to treatment. And some mathematicians had developed some probabilistic models to try to understand why that would occur. I'll give you a simple example, actually is something that I want, I think, to understand very easily. It's Lurie Millbrook in the 40s. They won a Nobel Prize. One of the biologists, one or a doctor, and one is a mathematician. And the reason why they won the Nobel Prize is because up to that point resists the development of resistance to antibiotics is a major problem. Still today, and up to that point, it was thought that resistance to the antibiotic was due to using antibiotics. Well, it turns out actually it was mathematics, really, that helped us discover that that is a part of why it happens, but actually usually not the main cause. In fact, in a sense, the resistance to the antibiotics is already present before you start the treatment. And it's because it's usually due to a mutation. And so it's really a function of how big is your index was bacteria's, how big is your population? And the more bacteria you have, you know, the larger is the population, the higher is the probability. Among them, there is going to be one bacteria with the wrong mutation just by chance. You know this, but I knew nothing about the antibiotic was going to receive, right? But just the wrong mutation. When you have millions or billions of bacteria, the probability to some of them may have their own mutation it's quite high. Now you introduce the treatment, and guess what, everyone you know who dies, but this one? So this type of work and some …. this work is what inspired me to do my part is math in cancer.

Karie Dozer [00:10:42] Are most people surprised when they find out that your background is in math and not in science, per se?

Dr. Tomasetti [00:10:48] Oh yeah. I mean, this is two summits. You know, how can you say anything about cancer? You didn't go to the school of medicine, right? But then? Well, for example, right before moving here, I was an associate professor in the Department of Oncology at Johns Hopkins, which is a very good school, a very good university cancer center. This has to do with what I was mentioning before, which is today understanding reality is become so complex that there are many questions that can only be asked where we tools there are mathematical in nature. We hear a lot about A.I., for example, right? So you may have an engineer that, you know, that doesn't even need to have a driver's license. Technically, as long as he understands, you know, neural networks and so on, he may be able to build. I mean, I make an extreme case, but the point is the part is mathematical. Here, it's so large that it certainly makes sense in today's scientific fields. You need a major effort by mathematicians if you want to make process progress. Otherwise, you're not even going to understand the sequencing data you get.

Karie Dozer [00:12:06] What does it mean to have a population like that at City of Hope and the research power at TGen to combine to answer these questions?

Dr. Tomasetti [00:12:16] Yeah, that's obviously it's fantastic. It's I will mention names, but I was considering other opportunities very well-known places to do research. In a sense, I give up maybe what academically would be the dream position of any professor of any field. But I did I because I felt that if I followed that direction, I would have done. I'm sure lots of cool things would have been just a typical professor. And what I feel TGen and city of hope are providing me here is with the opportunity to do something that really has it can have a major impact on the on the population in terms of cancer mortality. What I love Anti-genocide, there is essentially no red tape. It's really amazing that you have to and to really understand how cool it is and how people relate to each other. I've been in, you know, my poster was at Harvard, I was at Hopkins, the typical setting where every professor has his lab. And you know, you have some very famous professors and they don't talk with each other who they are competing against each other, you know, this is. And the red tape bureaucracy, this is this just all out of the window here. And the focus is let's get this, you know, done and let's make this happen. You know, a lot a lot of research runs into the risk of becoming a paper and that maybe someone may read and really have no impact on patients. Here I get, you know, it's the opposite here. It's all about having an impact. And the paper comes, it's important that we do that, but that's not the goal.

Karie Dozer [00:14:18] Do you ever wonder what you would be doing today if you hadn't made the decision to practice math for science sake?

Dr. Tomasetti [00:14:27] That's a great question. I think if I didn't decide to do the, you know, to apply my to medicine, I guess there would be two options. I've been to one or two places. Either I would be in Italy, probably teaching math to in high school or where I was where I started. You know, whether it was Central Bank or the European Central Bank or a major financial institution, I think I think that would have been, you know, this would have been the two most prevalent options.

Karie Dozer [00:15:05] And yet now you're talking about curing and preventing and detecting cancer early, which is a pretty big switch.

Dr. Tomasetti [00:15:12] I agree. It sounds kind of incredible. But life, I think, is the beauty of life that when you follow your passion and I have to say, I'm Italian and I love my country, I always miss all of that. But the United States is it's an incredible place in terms of the opportunity that provides you to really, if you want to accomplish and try to reach a goal to really open doors for you and give you those opportunities. So yeah, I'm living and living my dream.

Karie Dozer [00:15:44] What would you? Is there anything that you would want people listening to know about? The future of cancer research at TGen, whether it is on the detection and prevention side or whether it is on the side of proposing a better, more personalized cure, what would you want people to know?

Dr. Tomasetti [00:16:03] Well, first of all, I want people to know that I hope this doesn't sound just cheesy, but I feel people really care. I think people don't come to teach and if it's about themselves. I think people come to teach. And as I said, if they want to have an impact, it's really, I think the name that Jeff chose when you know this since it was founded, is perfect. It's translational. That's 100 percent the focus here. My dream is if five years from now, this blood test is available and people are using it and going to the doctor once a year, and we are finding cancer at the early stages and we literally like go from, you know, terrible mortality rates. We still have today to significantly smaller ones. I will feel I have reached one of my major goals and independently of whether this happened, you know, specifically through my effort or as part of my efforts. It's and everything but in science and in any field happens because of having a fantastic group of people working together. So it's never about one person.

Karie Dozer [00:17:19] Dr. Christian Tomasetti, welcome again, and thank thanks for your time today.

Dr. Tomasetti [00:17:23] Thank you very much.

Karie Dozer [00:17:26] TGen, the Translational Genomics Research Institute is an Arizona-based nonprofit medical research institute dedicated to conducting groundbreaking research with life-changing results. TGen is an affiliate of City of Hope. You can find more of these podcasts at TGen.org/TGen Talks or on Apple Podcasts. For TGen Talks, I'm Karie Dozer.