In this talk, Dr. Levi Garraway, director of the Center for Cancer Precision Medicine at Dana‑Farber, explains the emerging field of precision oncology—treating each cancer based on the unique genetic and molecular alterations of an individual’s tumor. He uses a Hobbit‑dragon analogy to illustrate how identifying a tumor’s specific “weak spot” can guide targeted therapy. Garraway outlines the limitations of traditional site‑based treatment, the development of Dana‑Farber’s enterprise‑wide “Profile” program that reads actionable gene alterations, and how such data can both select effective drugs and avoid ineffective, toxic ones. He highlights early successes, stresses the need for systematic, cost‑effective studies, and describes future priorities: re‑biopsying resistant tumors, expanding profiling beyond DNA, ex‑vivo drug testing, big‑data/computational pipelines, and translating complex biology into actionable decisions for busy clinicians. Concluding with a hopeful vision, he frames the center’s work as an “engine of hope” that aims to bring durable cancer control to patients worldwide.
Chapters
Good morning, everyone. I'm Levi Garraway, and as Alan said, I direct the new Center for Cancer Precision Medicine at the Dana-Farber. And as you also heard, precision medicine may be a term that's unfamiliar to many of you, which is actually okay, because the term didn't even exist until about 3 or 4 years ago. So the idea really refers to the goal of treating cancer based on the specific genetic or molecular alterations that arise in each individual tumor. And the underlying concept here is that cancer arises and persists because of mutations, changes in the DNA of cells that cause those cells to grow and spread when they shouldn't, and then other changes that prevent those cells from dying when they should. Now, maybe I should step back a little bit because I realize that at 8-something in the morning, If I start plunging into wonky terms like mutations and DNA and cells, I may lose some of you. So maybe I should take a nontechnical analogy to make it clear. So in about a month or so, my son, my 12-year-old son, is anxiously awaiting the third installment of The Hobbit movie series. This is year 3. And it's my job as a dad to take him to that. And some of you may recall, if you admit watching the second version, which was last year, there was a scene in which the Hobbit sees the dragon for the first time. And the dragon stands up and spreads its wings to show how powerful it is. And the Hobbit looks and sees that there's a defect, a chink in the armor right over the dragon's heart. So right there, you know how the whole story's gonna end. Somebody's gonna shoot an arrow through that dragon. It's gonna take 3 hours for it to happen in the next movie. But someone's going to shoot an arrow through the dragon's heart, it's going to fall to the ground, and everybody lives happily ever after. So precision medicine is seeing the dragon, seeing the monster of cancer clearly for the first time in a way that we can pinpoint weaknesses, and then going to our arsenal and drawing new drugs and attacking those weaknesses in hopes of hopefully bringing the dragon to the ground. So that sounds pretty good, but as we all know, the reason why we're here is we haven't always been good at doing that. And the challenge has been many, but one of them is that cancer is typically treated based on where in the body it occurred, but not necessarily based on the scientific insights about why it's a cancer in the first place. And the other problem is that we often don't have drugs that, even if we knew this, that could exploit that. And Dr. Bradner, who you'll hear later, will tell you about how we get some of those new drugs, but even before that, we need to understand, well, how do we even know how we would use those drugs? How would we know how to predict which cancer is going to respond and which one's not? So, as you might imagine, the core of this, or at least the guiding principle that we have been working with, is that we need to find a way to extract and interpret the relevant genetic and molecular information from each tumor. And for a long time, that was a major challenge. It was too expensive. It was completely inefficient for clinical implementation. There were too many logistical challenges. But when I had an opportunity to join the faculty at Dana-Farber several years ago now, one of the things that we realized was that the new technologies for interrogating cancers and genomes, et cetera, turned out to be surprisingly malleable. We could adapt and configure them to read out what we call actionable gene alterations in cancer with surprising ease. And when I say actionable, what I mean is a genetic change that might tell us, oh, this is a drug that could work, either a drug that already exists or a drug that's in clinical trials being tested experimentally. So that recognition and the sort of proof of concept around that, to channel something Ed just said, it showed us something that we didn't know we needed until we started doing it. And to Dana-Farber's credit, they seized on this vision and this opportunity immediately, and they invested considerable resources, aided in large part by many in this room, to make it possible so that any patient who comes to the Dana-Farber could have an opportunity to have relevant genetic information read out from their tumor. And that project has been called Profile. So it's an enterprise-wide effort to make sure that any patient where there's sufficient tumor material could have a chance to have a robust set of gene mutations readout that could either be actionable around new drugs or emerging drugs or biologically informative. So when you have that information, things start to get very interesting. Now one can look at that profile, one can look at that readout, and often see, okay, well, this, this is a particular drug I should use. And sometimes these are choosing from drugs that are already available, drugs that are already part of the standard of care. But more and more, these— this information can awaken us to opportunities for new drugs or drugs that we might never have thought about in a particular cancer type, or drugs that are out there in development and the drug company hadn't thought about how to use it. But this is exactly what we need to do, and there are anecdotes abounding for successes in this area. The other point about this kind of information, which sometimes doesn't get expressed, is that genetic profiles can also tell us what not to do, so they can often inform about treatments that we should avoid giving. So sparing toxic therapies that aren't likely to be effective in patients can be just as important as picking the right therapy. So there's really two sides of what can happen here. And what's exciting is that the evidence slowly but surely is growing in support of this precision cancer medicine paradigm. There are cancers like lung cancer where already there's rapid movement to incorporating substantial profiles of gene mutations. And there are many others where the genetic research tells us, well, this really should work, and it's just a matter of getting it out there, and there are anecdotes that are starting to grow. But I will say that the next 10 years is absolutely critical, because what's needed now is thoughtful, systematic, carefully done studies that really teach us how to use what is a lot of complicated information how to deploy it thoughtfully and carefully in a way that's going to be maximally effective and cost-effective. But that really is what not only Dana-Farber is all about, but really gets to the core mission of our new center, our Center for Cancer Precision Medicine. The goal of our center is really to elucidate how to bring this paradigm forward, and not only how to bring it forward to our patients at Dana-Farber, but eventually to the world. And there are several ways in which we are trying to do that. The first is to be able to study patient— the tumors that often really cause us the most problems, and that really involves reprofiling, re-biopsying tumors that have maybe had responded for a while to treatment but now are roaring back. You know, those are often the cases where really now our hands are tied. We don't really know what to do. There's an urgent need to learn how to treat those cancers better, what kinds of new therapies and combinations are going to work. So that's one area. Another area is to keep on pushing the technology, the technology that got us here in the first place. There— it continues to race ahead. I've mentioned a lot about DNA, but there are a lot of other molecular changes in tumors besides DNA that can tell us what kinds of drugs should be given, and we need to get out ahead of that. There are also new technologies that can allow us to grow cancer cells outside the body and potentially treat them with drugs and figure out which drugs might work. So these are things that we need to get our hands around as well. We need to bring in big data, new computational methods to teach us how to think about this data. There's far too much data for the human brain to process. We can't do this without the assistance of tools. There are outstanding faculty at the Dana-Farber who can help us do that. And most importantly, we need to bridge the gap, the gap between deep biological understanding and the ability for a doc who has a very busy a busy patient schedule to interpret that and be able to make the decision and actually take the action, get the drug to the patient. Bridging the gaps is what we at the center in Dana-Farber are going to be all about. So in summary, precision medicine is really about the actualization of rational therapeutics, bringing science fully to bear as we guide our treatment. But I would say that it's more than that. When I think about the work that we're trying to do to put the key elements together to make this happen, we're not just building a precision medicine engine, we're building an engine of hope. And Christopher Reeve, who was Superman when I was a kid growing up, had a quote which was, "If you choose hope, anything is possible." It's not going to be easy. We too often, we can wound the dragon but not slay the dragon, but we feel comfortable setting our goals high and really using precision medicine and other things that you're going to hear about from my colleagues to bring durable control to as many patients as possible. And I'm so grateful to be at Dana-Farber where it's leading the way. Thank you for listening.
