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Precision Medicine and the “Moonshot” Program
Nancy Davidson, M.D.
January 21, 2016

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Nancy Davidson, M.D., is director of the University of Pittsburgh Cancer Institute, where she also is a distinguished professor of medicine and associate vice chancellor for cancer research. She also serves as president-elect of the American Association for Cancer Research, the first and largest cancer research organization in the world. Dr. Davidson is a world-renowned breast cancer researcher who has played a key role in discovering how hormones, particularly estrogen, affect cell growth in breast cancer. Listen to the podcast to hear Dr. Davidson explain:

  • what the American Association for Cancer Research is and what its goals are
  • what precision medicine is
  • what she thinks the moonshot program to conquer cancer will do
  • what new treatments she sees coming in the near future

Running time: 11:25

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Jamie DePolo: Hello, everyone. I’m Jamie DePolo, the senior editor here at I am thrilled to welcome to our podcast today Dr. Nancy Davidson. She’s director of the University of Pittsburgh Cancer Institute, and she’s also a distinguished professor of medicine, and associate vice chancellor for cancer research. She also serves as president-elect of the American Association for Cancer Research, the first and largest cancer research organization in the world. Dr. Davidson is a world-renowned breast cancer researcher who has played a key role in discovering how hormones, particularly estrogen, affect cell growth in breast cancer. Dr. Davidson is one of the speakers at the Cancer Precision Medicine Conference, which is being presented by the Philadelphia Media Network and the American Association for Cancer Research. Dr. Davidson, welcome to the podcast.

Dr. Nancy Davidson: Thank you very much. It’s a thrill to be here.

Jamie DePolo: So, some of our listeners may not be as familiar with the American Association of Cancer Research as they are with some other cancer organizations. Can you tell us a little bit about the organization, since you’re the president-elect, and its goals?

Dr. Nancy Davidson: The organization was founded over a hundred years ago, and it brings under one roof the many, many, many people who are dedicated to the prevention and treatment of cancer. That includes basic scientists, clinical scientists, patients, trainees, senior scientists, anybody who has as their mission, their personal mission, to do something against cancer.

Jamie DePolo: Okay. So, it’s mostly professional people that are members, is that correct?

Dr. Nancy Davidson: It is in fact a professional organization, although obviously it embraces people at all levels, and we have a large advocate membership and aligned individuals as well.

Jamie DePolo: Okay. Okay. Now you’re speaking at the Cancer Precision Medicine Conference. I’ve heard several different definitions of precision medicine, from both doctors and advocates. To you, what is precision medicine?

Dr. Nancy Davidson: I think that precision medicine is the opportunity to take the newer insights we have about, in the case of cancer, the molecular changes that lead to the development of a cancer, realizing that all cancers are a little bit different, and then also thinking about what we know about the host. So I hope that precision cancer medicine is going to incorporate knowledge about the cancer, and knowledge about the person in which it resides, in the hopes that we can provide the most targeted, the most precise therapy possible.

Jamie DePolo: Okay. Is it mostly based on genetics, or are there other components?

Dr. Nancy Davidson: Well, I think that the earliest work has really been done on the genetics of the cancer, thanks to the big national effort, the Cancer Genome Atlas. You know, we now have a nice blueprint for the genetic changes that we see in many kinds of cancers, including breast cancer. So that’s the easiest place for us to start. But I think with time we’re going to find out that we’re going to use epigenetics, we’re going to use proteomics, metabolomics, so I think we’ll see lots of ways of trying to be more precise about our approach to cancer.

Jamie DePolo: Can you, just to help me out a little bit, explain just briefly epigenetics and proteomics?

Dr. Nancy Davidson: Yes. So, genetics has to do with the fact that there can be mutations or changes in DNA sequence that characterize many cancers. But it also turns out that sometimes we can see changes that are called epigenetic changes, which change the way that the DNA is transcribed into the RNA and ultimately into the protein, without actually changing the sequence of the DNA. And the reason why we think these changes might be important is they’re potentially reversible. It is hard to fix a mutation. It is possible to think about changing an epigenetic modification. And so there’s a lot of work looking at epigenetic modifiers as a way of trying to treat various cancers right now.

Proteomics refers to the notion that we would be able to look at protein profiles, that we imagine that one of the things wrong with some cancers is they make proteins in the wrong way. Either the wrong proteins, a mutated protein, the wrong amount of protein. And so proteomics might allow us to look at these protein panels in a combination way.

Jamie DePolo: Okay, and then possibly correct that.

Dr. Nancy Davidson: Well, to think about what it tells us about the behavior of the cancer, and what we might be able to do to modify it to intervene.

Jamie DePolo: Okay. Okay. Now, Vice President Joe Biden was just at the University of Pennsylvania to talk about the moonshot program to conquer cancer that the president talked about in his State of the Union address. For you, given your role as a researcher, what does that mean, you know, for cancer in general, and is there anything that it means for breast cancer specifically?

Dr. Nancy Davidson: I listened to the vice president’s commitment as a researcher, as a physician, I’m a practicing oncologist, as the sister of a person who died of nonsmoking lung cancer. I mean, I think that there are a lot ways you can listen to this. I’m excited that somebody with Vice President Biden’s stature and with President Obama’s backing is taking on this initiative. As I understand it, as he’s putting it together he hopes he’s going to be able to galvanize a lot of collaboration across the many constituencies that are dedicated to trying to eradicate cancer. But of course we hope that he’s going to be able to help us to garner some of the resources we need for things like NIH funding. I think his work is in early days now. But my sense is he’s been very effective over the years in trying to build coalitions, and so we’re excited that he’s going to take this on.

I don’t think that there’s necessarily going to be anything specific to breast cancer or lung cancer or colon cancer. My guess is this is going to be an effort that’s devoted to all cancers -- and that’s a good thing, because I think there are so many things that characterize cancers that are true across all sorts of cancers. So, anything we learn in one cancer is going to be beneficial for another one.

Jamie DePolo: So that kind of plays into the idea that I’ve seen with some of the, what people are calling basket studies, where they’re not studying, say, just breast cancer. They’re maybe looking at a specific mutation that’s common to a breast cancer, and a lung cancer, and a prostate cancer, and looking at a treatment that might be effective for all of them. Is that kind of where you see the moonshot idea going?

Dr. Nancy Davidson: I think that’s certainly a part of it. I think one of the things we’re learning right now, that we’re focusing not only on anatomy, where did the cancer start from, what was the tissue of origin, and we’re also focusing on the pathways. What are the pathways that are abnormal? So I think that we had thought perhaps at one point that if a pathway went awry, if it went awry in a breast tissue or in a melanoma tissue or colon tissue, it wouldn’t matter. But these basket trials are actually teaching us that it probably is a combination of both the anatomy and the pathway.

For example, in the cancer world there’s a kind of mutation called the RAF mutation. And it looks like if you have a RAF mutation and certain kinds of melanomas, you’re really very susceptible, in a good way, to certain kinds of anti-RAF treatments. But the same kind of mutation that’s in a colon cancer, no response to these anti-RAF drugs. So it’s going to a combination, it turns out.

Jamie DePolo: Okay, so it’s both.

Dr. Nancy Davidson: You know, maybe we’re not surprised. Cancer is not easy, right? If it was easy, we wouldn’t be sitting here having to talk about it.

Jamie DePolo: Right. Right. Right. Okay. Oh, I know, one thing, too, does the idea of the moonshot or this new sort of -- heading toward curing cancer is what they’ve said -- is prevention a part of that as far as you know, or is it really focusing more on treatment and eradication?

Dr. Nancy Davidson: It’s early days, but I surely hope it’s going to include the whole continuum of cancer. Because I think that, you know, the best cancer of course is no cancer, and so anything we can do to try to prevent cancer is going to be extremely important. I think early detection is still an important component for many kinds of cancers, and that hasn’t gone away. And so I hope that we’re going to be able to address the entire continuum from prevention all the way through to on the other end, survivorship care.

Jamie DePolo: Okay. Perfect. Now given your role as a researcher and an oncologist, do you see new breast cancer treatments in the future? Are there things coming up that you’re excited about, or things that may be coming up, say, in 5 years that you’re excited about?

Dr. Nancy Davidson: I think we’re excited about a lot of things. You know, first and foremost, for a long time, of course, we’ve treated breast cancer with hormone types of therapies, and they’re still a mainstay for us. I think what we’re beginning to learn is more and more about the kinds of resistance mechanisms that might come up to hormone therapies. And so that allows us to think about ways that we might be able to prevent that resistance or overcome that resistance. So that, I think, is going to continue to be a hot area. You know, the drug palbociclib was approved in the last year or two, a cyclin D-inhibitor, a cyclin DK-inhibitor, and so I think we’re going to see more of that kind of work in the hormone camp.

A lot of interest in whether or not we can improve even further with the anti-HER2 therapies, and of course, a lot of traction has been made there. That’s a form of breast cancer that really has quite a lot better outcome than it used to have because of the several drugs that we have available. So more interest in trying to develop other agents, and also to try to think about mechanisms of resistance.

And then the last part, of course, our really tough nut to solve, is the triple-negative breast cancer world. And we’ve come to learn that those triple-negative breast cancers actually come in several different flavors, right? There are a lot of different subtypes. And so I think that gives us the opportunity to think about whether or not we can have targeted therapy that’s going to be good for a subtype of a subtype. And that’s probably where we’re headed in a disease like cancers generally, and breast cancer specifically, that what was once one disease is actually now recognized to be a whole variety of distinct diseases that happen to arise in the breast.

Jamie DePolo: So, in the future somebody probably isn’t going to say just, “I was diagnosed with breast cancer,” it would be, “I was diagnosed with this subtype of triple-negative breast cancer,” in theory.

Dr. Nancy Davidson: Well, I think the consumer might say to herself or himself that I was diagnosed with breast cancer, and that may be sufficient for a lot of what you need to do in life. But certainly from the medical perspective, I think ultimately you’re going want to know a little bit more about it, because it’s going to dictate the kind of therapy that you get. And so, certainly, the medical team wants to know about that, and I think probably the patient does as well.

Jamie DePolo: Okay, and one last question: What about metastatic disease? Do you see any new treatments on the horizon, any new things coming up for metastatic disease? Or does all of what you talked about before sort of play into that as well?

Dr. Nancy Davidson: I think that it does. You know, our standard way of working for a long time has been to try many of our new ideas in the setting of metastatic breast cancer, and I don’t think that’s going to change dramatically. So, I think that women who have the misfortune of having metastatic breast cancer are often amongst those who are given the opportunity to receive a new therapy, you know, at its very earliest phases, and sometimes those women can really profit from that kind of therapy. So all of the concepts you and I just talked about are very much operative in metastatic breast cancer. And we hope that the insights that we would make there will be helpful, not only for those women, but also where possibly we might be able to take them back into earlier phases of breast cancer.

Jamie DePolo: All right, Dr. Davidson, thank you very much. We’ve been talking to Dr. Nancy Davidson, who is the president-elect of the American Association for Cancer Research, as well as a researcher and oncologist at the University of Pittsburgh Cancer Center. Thank you so much.

Dr. Nancy Davidson: Thank you very much for the opportunity to speak with you, Jamie.

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