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How does cancer grow? Why do some cancers react positively to treatment while others seem to resist? Understanding these relationships, the genetic events and cell-to-cell interactions that lead to cancer, not only can provide better understanding of how cancer develops, but also drive potential new targets for drug development. Understanding these relationships also essential to the incredible work being done by Dr. Ben Ho Park.
Dr. Park was recently appointed as co-leader of the Breast Cancer Research Program, Associate Director for Translational Research, and Director of Precision Oncology at the Vanderbilt-Ingram Cancer Center in Nashville. He’s been a BCRF investigator since 2008, and as you’ll hear at the top, he also has a unique creative talent that surely won’t directly lead to solving breast cancer, but it does to seem to make his lab an engaging and fun place to work. And who knows, perhaps in some way that creative culture is part of what inspires Dr. Park’s creative research approaches.
Read the transcript of the conversation below:
Chris Riback: I’m Chris Riback. This is Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation in conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship, and metastasis.
Dr. Park, thanks for joining me. I appreciate your time.
Dr. Park: Thank you very much.
Chris Riback: I get to do a lot of these conversations and they’re all fascinating, but yours is the first one where I really have to start not with the groundbreaking life-changing research, your life’s work, and all of that, but instead, with nicknames. You have some interesting people working in your lab. Apparently I am talking to Dr. Ben “Tally” Ho Park, and among the folks you work with include Sarah “bellum” Croessmann, Mark “of the Covenant” Rosen, and Jenna “if you can, I” Canzoniero. I mean, these are top-notch nicknames, Dr.
Dr. Park: Yeah. I’m quite a fan of puns, and some of those come very easily. Some of them I’ve actually worked at. Some of them, between you and me, are just really horrible.
Chris Riback: We didn’t mention those. They were pretty good.
Dr. Park: I have been known to revise some of them. My favorite one though was I had a graduate student, an MBP student a number of years ago, and her name was Grace Kim. And I called her Grace “for the Cure” Kim. I thought that was perfect.
Chris Riback: Oh, that is really good.
Dr. Park: But I unsuspectingly demand some sort of silly picture. If they don’t take it I will just snap one with my iPhone and put it up there and threaten them with that. Most of my trainees are well aware of this.
Chris Riback: Silly photos are quite the threat. But it was fun to read, and I was trying to think through, about the personalities behind it. It gives off a real sense … I’m sure exactly what the type of place that you run, which is working hard but a bunch of people who have some personality and fun behind them. So, good for you. It must make every day that much more enjoyable.
Dr. Park: I think you know the work hard, play hard philosophy is really strong within our group and our lab. I’ve always felt like we have to take the mission seriously and the job seriously but we don’t have to take ourselves that seriously. And I think that served us well.
Chris Riback: That’s well put. Yeah. Anyhow, the serious work is evident, and it’s evident in the results. Let’s talk about that for a second. Let’s turn to the research.
Dr. Park: Sure.
Chris Riback: How does cancer grow?
Dr. Park: Well, you know, it’s more of a complicated question than one might actually think. Superficially, we know that cells divide, and cells are the building blocks of our bodies. Each of our bodies have trillions of cells and they’re all very tightly controlled, in terms of how they grow and how they don’t grow. Those are two equally important parts of the equation.
And so cancer cells can grow because one of those two areas becomes faulty, meaning that cells abnormally can proliferate and/or cells can abnormally not proliferate, meaning that they should stop growing but they don’t in cancer, when they really should. And so we think of that in terms of both accelerators and brakes. So you could either press the accelerator and the cells start dividing, or you can disable or have faulty brakes, and in that case the cells will continue to grow when they shouldn’t.
But there’s even more components to that. Cancer cells not only grow, they spread. That’s what we call metastasize. And really, that’s what kills patients, is when cancer spreads to distant organs and starts taking over, if you will.
So those fundamental ideas and concepts of how cancer grows, spreads, and kills patients really has dictated our thinking for the better part of 40 years or more. And dictates our thinking in how we’re going to attack cancer.
Now we know even more, because what causes the abnormal growth or the abnormal faulty brakes is really a series of genetic events. Each one of our cells has DNA, and DNA is a blueprint of our cells. And what cancer really is are mistakes of DNA. It’s almost like our bodies are trying to evolve to be immortal and live forever, but unfortunately they do so at the cost of the host. And so, that kind of process where you have, some folks in our business call it clonal evolution, where you get one mistake that gives it a slight growth advantage and then you get a lot of cells that grow a little bit. You might think of that in terms of like a polyp for colon cancer, but that’s not cancer yet. But then any one of those cells can get another genetic hit or mutation as we say. And that gives it another growth advantage, so that now it can become a cancer. And so on and so forth.
So it takes about, people estimate, five to eight of these DNA mistakes or mutations before you can go from a normal cell to a cancer cell.
Chris Riback: What if one catches such a cell in the first or third mutation? I fully assume that’s exactly what one tries to do. We try to catch it before it gets to that five to eight zone?
Dr. Park: Yes, exactly. That’s really where the focus is, on earlier prevention and screening. Using again the example of colon cancer, where we have a polyp; a polyp is a growth and it’s technically a tumor. A tumor really is just a growth, but it’s not necessarily a cancer. And so, if we can screen via colonoscopy and identify a polyp and remove it, then we’ve really reduced the chance of that polyp ever becoming a cancer.
Similarly, in breast cancer we have the equivalents of things that we call in situ carcinoma, and even earlier, some things that we call ductal hyperplasia. There’s also other variants called lobular hyperplasia. But the spectrum of normal to cancer falls along the same paradigm, and many patients in this country will get diagnosed with what we call ductal carcinoma in situ.
Under the microscope, the cells look cancerous, but they haven’t actually invaded beyond their normal ductal architecture. The breast tissue is made up largely of ducts and glands, and the cells that form the ducts are the ones that usually become breast cancer in most patients.
So, many patients in this country are diagnosed with stage zero breast cancer. That’s a real kind of misnomer and head-scratcher, because how can you have stage zero breast cancer? But that is ductal carcinoma in situ, and it’s treated locally as if it were a cancer, because we want to catch it and cure it before it actually does become a cancer.
Chris Riback: Let’s focus on what’s going on inside and among the cancer cells, because there are some things that you’ve written that just sound fascinating and confusing for somebody like me, but important no doubt.
So there are these cell-to-cell interactions and you’ve shown that … and I’m quoting here … “cancer cells with single mutations interact with neighboring cells, with other discrete mutations, to increase cancerous growth and drug resistance.” But here’s the key. These cell-to-cell interactions require physical cell-to-cell contact.
A moment ago you were talking to me about genetic changes, about DNA changes, and about those mutations and then ultimately and potentially, and one hopes not, metastasis. Here, the ways the cells, it sounds like, interact with each other and that the physical cell-to-cell contact is what matters?
Dr. Park: Well, this is a brand new area, and we haven’t published this yet, but we are getting ready to submit it for publication. But it is potentially a different way of thinking about how cancer evolves. And this is based upon on observations made by others as well as models that several groups have now shown.
Nobody has really taken human breast cells and demonstrated that there are specific mutations that are distinct in each of those cells but that the cells are otherwise identical, that grown separately have one type of behavior but when you mix them together have another. And that really kind of blows away our concepts of how cancers evolve, as the classic paradigm has always been what I just told you, how you get one genetic hit and then that grows. You get another genetic hit in the same cell … and we’ve modeled that as well. You definitely do see changes when you add on mutations within the same cell.
What was recently appreciated was that it looks like in some cancer patients, but not all … this is again, breast cancer … that we see different populations of cells or even what we call, sometimes sub-clonal populations of cells, where not all the cells share the same mutations, and some of the cells even have distinct mutations.
And so, it occurred to me that we have really good model systems to try to study this. But it also occurred to me that this is the type of stuff that if you were to try to put this through for traditional funding mechanisms, it would get killed and blown out of the water, because we don’t have, at least at the time, we didn’t have enough preliminary data to demonstrate that this was something that we could really, at the end of five years, show that we had something. And so, I think the nature of foundations like BCRF that grant these types of programs to investigators, not necessarily to the project, per se, but more about investigators, and we described what we were working on at the time. That really has been essential to our ability to move this project forward.
And so, this is exactly what you were saying. We were very, very surprised to discover this, that if we mix up cells that one of the cells confers a growth advantage to the other cell. And again, that’s mind-blowing that you could actually think about that there could be two populations of cells and it’s actually the physical touching of those two cells at their outer surface or the membrane, as we call it, that confers this advantage.
We’re working on exactly how this happens, and we’ve got some clues. But this is also an opportunity for thinking about how you would drug these cells. As an example, you might have a drug against one of the mutations, in this particular case, something called PIK3CA versus another drug that hits the HER-2 population. Historically, when we’ve looked at patients’ tumors that have … let’s say 10 percent of the population has the PIK3CA mutation and 90 percent has the HER-2 mutation, we might not think about targeting the PIK3CA, because that’s the minority subpopulation. What we’re discovering and kind of working out in these models is that thinking may not actually be correct, meaning that you could attack the HER-2 population but that would get rid of everything, but that’s the dependent population on the PIK3CA population. So in fact, even though it’s 90 percent, it’s getting its growth properties from that minor population. And so, it now makes more sense, having that knowledge, we should be attacking that minor subpopulation of cells. And that’s again, very, very different than what we would normally do.
Chris Riback: It would be a massive rethinking. It would be a massive rethinking.
Dr. Park: Exactly. And so that’s kind of why we were very excited about this, because maybe it affords us an opportunity to think about how cells are dependent upon one another, but you could kind of hit it at the roots, if you will, the thing that’s really causing the growth, the population of cells, that is. And that may also be one of the reasons why there’s resistance to therapies. It’s not really resistance, you’re just not getting the right clone or population.
Chris Riback: That’s what I was going to ask you was what got your brain thinking in this way? It forces you, or I guess you were forced, to think in a differentiated way, in a way, as you kind of described, that runs counter to decades of thought. Was it something that you saw or was it something that you didn’t see, because you just raised drug resistance, which was something I wanted to ask you about. I know that’s an area that you-
Dr. Park: Yep.
Chris Riback: -have studied. And so, was it more that you saw something or was it that you’ve looked at drug resistance and thought about drug resistance and you’re just like, Man, this doesn’t make sense. Why do some therapies work in some cases but not in other cases?
Dr. Park: You know, it’s a little of both. It’s a combination of having patient data, seeing patients, getting their tumors sequenced, understanding that there are all these subpopulations that sometimes it looks like there’s two totally independent tumors, and that’s also different in our thinking from traditional standard approaches, or the paradigms that we’ve been used to working with.
But it’s also seeing patients develop drug resistance, and then seeing what’s left behind afterwards. So it’s really combinations of both that kind of forged our thinking into hypothesizing that maybe there’s more to this than what we have really thought, that our models and ideas have been a bit simplistic. In fact, we know that cancer is a very complex disease, that there are many different types and there’s many different ways to get to becoming a cancer and becoming metastatic disease.
That’s really where I think there’s the advantage of having opportunities like BCRF to say, You know what? We know that this could be construed as a crazy idea, that this is not conventional thinking, but you know, this is how discoveries are made.
And you have to do some high-risk high-reward research in one’s portfolio if we’re really going to dramatically move the needle forward. So I’ll be the first to tell you; I don’t know whether this is really going to pan out to be a hugely paradigm-shifting way of thinking of all cancers. I actually don’t think it’s going be for all cancers. But I can tell you, based upon sequencing efforts from breast cancer patients and their individual metastases, we do see this sometimes, and that did inform these experiments.
Chris Riback: Where are you on that? Where are you on that experimentation?
Dr. Park: Well, this is being led by several students in the lab right now. Our hope would be that we can wrap this up in the next few months and submit it for publication somewhere.
But the cool thing about this is that one of the things that my students have done, they’ve now labeled cells with, we call them fluorescent proteins, so you can actually label the one cell with the one mutation green and the other cell with the other mutation red. We’ve made these really awesome movies, and I hope that once this is published, I can put them up on the webpage for BCRF, because you can see how the one population, the red cells in this case, if they’re not touching any of the green cells, in the middle of the movie, on the screen, they just stay dormant. And then as soon as the green cells are growing and they touch the red cells, the red cells start taking off.
Chris Riback: That would be-
Dr. Park: Yes, pretty cool.
Chris Riback: -really cool. And also really helpful to communicate the point, because what you just described in a movie in red and green cells and watching them interact or not … I mean, we can all get that.
So I saw a quote of yours at one point, where you worried potentially that perhaps we are overtreating breast cancer. What did you mean by that and do you have that concern? Was that the right word?
Dr. Park: You got it; you nailed it. But it’s not just me. All medical oncologists who treat breast cancer and other types of cancers are worried about this. Not worried in the sense that are we overtreating? Undoubtedly and unequivocally we are overtreating. We worry about the side effects and toxicities.
The paradigm of how we treat early stage breast cancer patients, early stage colorectal cancers, some lung cancers, is that we do surgery … I mean, for early stage solid tumors, the intent is usually cure. And so, we always say that there’s one shot at cure, meaning that first solid tumors, like breast cancer, it’s a local problem, meaning that the tumor is in the breast. We need to get rid of that, so we can do that with surgery, and then sometimes surgery with radiation. That can take care of the local component.
But then there’s also the systemic component. That is what if cancer cells have now gone into the circulation and what will happen is, with time, if they’re left untreated, they will become distant metastatic disease, which is not curable.
And the reason for that is, because as I was telling you before, cancer is really the accumulation of multiple mistakes in the DNA, but it’s not a static process. All cancers to some degree have what we call genetic instability, and that’s what drives all these mistakes, but it also drives all these subpopulations and what we call tumor heterogeneity. The soonest that we can detect cancer when it’s metastasized is about a cubic centimeter, and that’s already a billion cancer cells.
Chris Riback: Wow.
Dr. Park: And each one of those cells is different from each other. We don’t have currently drugs that we can throw at patients and cure metastatic disease to get rid of every single cancer cell, because there’s so many. There’s already drug-resistant clones, if you will, or cells that will grow out to become the new dominant population.
But, if you rewound the clock, before you got to a billion cells, before you can see the cancer metastasized … let’s say it’s 10,000 cells … therein lies the opportunity to try to eradicate microscopic systemic disease that would otherwise come back if left untreated. And that’s why we use multiple drugs after surgery, to treat and eradicate patients of microscopic metastatic disease.
So, that all sounds well and good, but here are the real numbers and facts. After surgery or local therapy, so surgery and radiation, the majority of early stage breast cancer patients in this country will be cured. Maybe 60 to 70 percent. And the rest, meaning 30 percent, let’s say, are going to have micrometastatic disease. If we treat with chemotherapy, hormone therapy, HER-2 directed therapy, depending upon the type of breast cancer, we can reduce that 30 percent, maybe by half, maybe more, depending upon the subtype. So now, rather than 30 percent of patients recurring with metastatic disease, we’ve chopped that down to maybe 10 to 15 percent.
Dr. Park: Again, depending on stage and the type of cancer. So there’s still a lot of patients that we’re not going to get, because 10 percent of breast cancer patients in this country alone annually, that’s going to be about 20 plus thousand cases of breast cancer that is going to come back as metastatic incurable disease.
We know that we’re curing this, because of these large clinical trials are recruiting additional patients with systemic therapies because of the large clinical trials that have randomized patients after local therapy, patients get randomized to placebo or chemotherapy. These studies take years to decades to complete. If you have enough patients, and enough follow-up time, you can show that chemotherapy, as an example, cuts the rate of recurrence, distant metastatic recurrence, by about 10 to 15 percent.
Now, that all sounds well and good. The problem is, when I see a patient in clinic for the first time, with newly diagnosed breast cancer and she’s just had her local therapy, I don’t know if she’s cured or not.
The majority of them are. But I don’t have a microscopic view or lens to let me know whether this patient actually has microscopic disease. So we tend to treat almost everyone. We treat 100 patients, let’s say, to save 15, knowing fully that 70 don’t need it.
Chris Riback: Because you can’t necessarily get that microscopic view at this point.
Dr. Park: You don’t know.
Chris Riback: You don’t know.
Dr. Park: And you get one shot at cure. So that’s why we overtreat.
Chris Riback: Yes.
Dr. Park: Now we’ve made some progress. There’s the oncotype test and others that can help us decide whether this is really a type of breast cancer that is going to recur in 10 years, and, I should, is it even sensitive to chemotherapy? But in my view, it would be great to augment such tests with real-time evidence that a patient does or does not have microscopic disease. And therein lies the first kind of utility that I see for so-called liquid biopsies, which also has been funded by BCRF in the past.
Dr. Park: Looking at what we call self-reDNA … it’s long been known that all of our cells, whether they’re normal or cancerous, shed or secrete small DNA molecules into the bloodstream. Nobody knows exactly what this is for. Some people have ascribed some function. Many people just think it’s a waste product, including myself. I like to call this “cellular poop.” I’ve said that in some lectures.
Chris Riback: That’s the technical, medical term. We all know.
Dr. Park: Exactly. It’s one of my favorites. The knowledge of this has actually been around for decades, but we didn’t have technologies that allowed us to really assay for this. And so, finally, over the past couple decades now, we’ve gotten better in terms of DNA sequencing and looking for small amounts of DNA in whatever source that we can throw at the machines. In this case it’s plasma, from the blood.
In fact, fetal maternal medicine, that whole field is about a decade ahead of us. There are now tests, believe it or not, where a pregnant mom can go to a doctor, get blood drawn, and have the fetal DNA sequenced from her blood. And so, we don’t have to necessarily do amniocentesis and other more invasive procedures to look for genetic anomalies of the unborn child. That has really revolutionized the field in terms of screening for genetic disorders.
We’re doing pretty much the same thing in our field, where we can now draw tubes of blood and find cancer DNA. The challenge though, for our field, has been making sure that these tests are going to deliver in terms of how they can guide our thinking and therapies for cancer patients. And that’s really where the idea of clinical utility comes in.
Dan Hayes, who’s also a BCRF funded investigator and former ASCO president … I always quote him, because he says a bad test can be just as dangerous as a bad drug. I think that’s really, really important and a powerful statement to remember, because we have to put tests or biomarkers as we call them, through the same rigor as we do for any drug, because you really want to make sure your test is going to be accurate in terms of who not to treat, versus who to treat.
And so we’ve, after years in the making, have really been the first to launch a prospective national multi-center trial, just like a Phase III drug trial, really to see whether we can use circulating cell free tumor DNA as a marker of residual disease for breast cancer patients. That study recently recruited patients. We’re following them up … this is again in early stage breast cancer and we, just like a drug trial, have to wait for follow-up data to really see whether this is going to work.
Chris Riback: You certainly don’t suffer from a lack of activity or a lack of things going on.
Dr. Park: No.
Chris Riback: And on top of all of that, maybe we can talk about you for a second.
Chris Riback: You throw on top of all of that, a terrific new role and a move into Vanderbilt. Congratulations on that, by the way.
Dr. Park: Yeah. Thank you very much. I appreciate it.
Chris Riback: I shouldn’t even say role, because you know, as one can judge by all the different things that you’re doing, you’ve got multiple roles. You don’t fill just one role. I bet you wish your life were that simple, just one role. But there is one role, or one aspect of what you do, that I want to ask you about.
Chris Riback: That’s the Associate Director for Translational Research. I have loved, in these conversations, learning about translational research, because it’s terrific to hear how folks like you take knowledge from one research area and translate it into clinical care, and get to see what’s going on and the back and forth. I assume that has to be extremely rewarding to see how research translates. What does translational research mean to you, and why are you drawn to it?
Dr. Park: You know, I think that is such a great question. It’s probably something we don’t ask ourselves enough of. Translational research can mean so many things to so many people.
My own view of this, or how I’ve structured my career, is really taking what I’ve learned, both in my training as a PhD scientist as well as an MD medical doctor, and figuring out, How do we take observations from the lab and address important clinical problems that our patients would benefit from? And then vice versa, when we see patients suffering from cancer and certain aspects of it, whether it’s disease-resistance or side effects from therapy, How do we tackle that problem from a laboratory perspective, to really have an impact? And so, those two are a back and forth, it’s not a one-way street.
But it really is hugely exciting to think about how we could affect and develop new standards of care, new discoveries that are going to help cancer patients, both in the short term and in the long term. And you know, my example of the liquid biopsies for self-reDNA really speaks to that. You know, this is something where we’ve been working on that for about 10 years now and I was fortunate in that Hopkins, my former mentor, Bert Vogelstein, really kind of defined and created that field.
I kind of just took off from it, because it was so new and it was right upstairs from my own lab. I remember the first time we did some patient samples, I was just amazed that we could actually detect microscopic amounts of cancer in the blood. I went up to Bert’s lab, I said, “You know, where we really need to focus, at least for breast cancer, is in the early stage for this over-treatment problem,” because I see so many patients struggling with this … are they cured? Are they not cured? You know, is the chemotherapy working? Do I even need it? These are fundamental questions that patients bring to us and really speaks to the unmet need that we tried to address with liquid biopsies in this trial.
It’s a long process to get there. I’m the first to admit it, but it is incredibly gratifying thinking about how discoveries in the lab have made impacts into patient’s lives with breast cancer. That’s how I view translational research.
I think my role here really also speaks to that, because I’m involved with various aspects of not only what we call wet lab research, where you know, we look at the bench and we pipette little amounts of liquids and enzymes into tubes and try to answer questions that way. But also the bioinformatics group here, the people who actually can take computer data and big data and make sense of it, is really just incredibly strong at Vanderbilt. It’s one of the best departments in the country, if not the world. And so, having that opportunity to interface with them and to also get to the clinical space has been hugely fun, in the very short time that I’ve been here. I view this as an opportunity, where I get to help direct and lead multiple different groups with incredibly world-renowned leaders into the problem of cancer. How do we use all the expertise and direct that into a focus that’s going to lead for benefit for our patients? That to me is hugely fun and exciting to be here.
Chris Riback: It’s got to be. And yes, there is so much going on. You touched on it. I mean, is there a more human question in the human anxiety and anxiousness that you, obviously, clearly, and people like you deal with every day, and want to try to relieve. But that question, Am I cured? Do I still have the disease?
That just goes to the heart of what you and people like you are trying to resolve. We think about it scientifically and medically and research-wise, but you really hit it, in my mind. At the core, there’s just a human question, Doctor am I okay? And that’s what-
Dr. Park: And it’s incredibly frustrating from a physician perspective not to be able to tell patients whether they’re cured or not.
That, I will tell you, is just as debilitating for many patients as having a diagnosis of metastatic disease, not being able to overcome the fear of recurrence. I’ve always been an advocate and proponent for patients to seek out professional help in that regard, because it is so difficult to live with that. You know, it’s like the Sword of Damocles, you’re just never sure when it’s going to fall.
The truth is, in the majority of patients, it won’t. It won’t come back, as I was saying earlier. It is still something that anyone could understand how horribly difficult that is to live with. And so, I’m hopeful that with better technologies, that our clinical trial and others moving forward in this space, will really be able to address that as well.
Dr. Park: I think again, that’s an important area where seeing patients has informed my direction in the lab.
Chris Riback: That’s wonderful. And you write about the psychological, if you will, but emotional and mental aspect of it, and I had a conversation on that with another BCRF investigator recently. Incredibly important work, as you identify.
To close out, how did you get into this in the first place? And I mean, going way back. I believe I read that you grew up in Michigan, which makes you another great Midwestern guy. But for you, was it always science? Was it puns? Was it potentially sitcom writing? Maybe a nickname writer.
Dr. Park: Maybe all of the above.
Chris Riback: Maybe all of the above. Well you did it.
Dr. Park: No, it was interesting. I grew up in this little town in Michigan called Saginaw, and I went to a public school system, that at the time wasn’t really the strongest academically and I ended up almost on a whim, applying for and getting accepted to U of Chicago, which is the complete polar opposite. I was not prepared for this. My first quarter I was pretty overwhelmed, But thankfully, I quickly caught up.
Part of my decision to go to medical school was based on the fact that my father was a surgeon before he retired, and it was kind of funny because he kind of discouraged us from going to medicine. He said this is a really hard life and you’ve got to be passionate about it and love what you do if you’re really going to do something like this. You can’t do it because you think it’s a safe secure job.
And I took that to heart, but I ended up making the decision on my own to become a pre-med. Part of becoming a pre-med, in most academic places at least, is that there’s what I like to call check boxes. You have to shadow physicians, you have to do some volunteer community work. And even back in the 1980s, you should work in a lab, at least for a summer, if not a year or more, kind of to show that you have some interest in academic research and biomedical research.
I started in a lab in sophomore year at the U of Chicago. Hans Schreiber, who still has a lab there. And I was fascinated. It was a tumor immunology lab and I just thought, Wow, this is incredible. And I met MD-PhD students. I met people who were actually physician-scientists, including Hans, who’s an MD-PhD himself. I heard about these programs that you could get into, to become MD-PhD physician-scientists. That really was my turning point. I really decided that if I was going to be a physician, I wanted to not just … I wrote this in my medical school essay, I’ll never forget it. I didn’t want to just treat patients, I wanted to treat the disease.
Dr. Park: Meaning that I wanted to figure out how to solve the puzzle of the disease, including cancer. So at a very early age in this stage of my career, I was exposed to cancer tumor immunology. My PhD is actually in immunology. I like to tell the story that at some point, I just thought, Wow. Tumor immunology is just too hard. This cancer immunotherapy is never going to work, so I left the field. And as many know, I was far from right in my prediction.
Dr. Park: In fact, tumor immunology has become one of the hottest areas. It’s taken several decades, but yeah.
I was fascinated by genetics, and so in graduate school, I was working on a retroviral project, where I was mutating genes in retroviruses. HIV was a very, very big area of research at the time and still is. And I got down to this point where I could define a pathogenic behavior of a retrovirus by mutating a single base pair or a letter of DNA, as we call it.
Dr. Park: That’s when all of a sudden my light bulb moment came on. I was like, Genetics is incredible. One change in the DNA alphabet leads to a black and white difference. And at the time, Bert Vogelstein was tearing up the field in cancer genetics, publishing high-profile papers, one after the next, defining really the genetic, genomic landscape of cancers, particularly colon cancer at the time.
I applied in the lab and I got lucky enough to get accepted. The rest is history.
I mean, it was such an elegant idea that not only could we understand cancer at the DNA level, but because it was a disease of DNA, that afforded us the ability to target, because those DNA changes are unique to the cancer cells, compared to the normal cells surrounding them. So, if you have an abnormal DNA gene or mutated gene, you, by definition, or usually, will have an abnormal protein, since DNA just really encodes for proteins. Therein lies the ability to target those proteins that are causing cancer.
Now we have numerous examples of that. I think that’s an area where I’m also trying to bring to bear here at Vanderbilt, in what we call precision oncology. This is also something I also started at Hopkins with our molecular tumor board, but I have the kind of capacity or ability here to really grow this to hopefully a world-wide level, where we’re going to have the ability to really affect patients who have these mistakes in their DNA, that we have drugs.
I think that’s one of the, again, hugely gratifying points of my job here, that we’re going to be able to reach out to more patients, get them in here, understand what makes their tumors tick, and then hopefully find drugs that will help them.
Chris Riback: Well, it’s very clear that sitcom writing’s loss was medicine’s gain. We’re glad to have you on this side of the screen. And thank you. Thank you for your work, and thank you for your time with me today, Dr. Park.
Dr. Park: Oh, thank you. It’s been a pleasure.
Chris Riback: That was my conversation with Dr. Park. My thanks to Dr. Park for joining, and you for listening. To learn more about breast cancer research or to subscribe to our podcast, go to BCRF.org/podcasts.
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