We often hear that medical research is approaching “breakthroughs” or is at a “tipping point” in innovation. But what does all that really mean?
Dr. Nancy Davidson, a longtime breast cancer researcher and leader in cancer studies, says we really are at a tipping point in cancer research, largely thanks to recent developments in the technology we use to understand and treat cancer.
Davidson is about to wrap up a year as the president of the American Association for Cancer Research. She gave her final address to the AACR Sunday at the organization’s annual meeting, and GeekWire sat down with her to get her take on how the field has developed in the last few years and what’s on the horizon for cancer care.
Davidson, who became president of the Seattle Cancer Care Alliance and the SVP of clinical research at the Fred Hutchinson Cancer Research Center in December, said there are two huge advancements in fundamental science that have driven recent innovation.
The first is the Cancer Genome Atlas, a project by the National Institutes of Health that cataloged the genetic changes in cells that lead to cancer. The second is CRISPR, the gene-editing technology that has spurred the widespread use of gene editing in research and treatments.
Together, Davidson said, these and other advances have led to innovations like immunotherapy and other creative, novel treatments that change how we are working to combat cancer.
She counted other successes in more effectively designed clinical trials and a focus on screening for — and taking measures to prevent — cancer before it takes hold and becomes difficult to treat.
“But we’re not done,” she warned. Even though cancer mortality is slowly dropping in the United States, “cancer mortality is ballooning across the world as we make inroads against other kinds of public health problems that people would be susceptible to, like infectious disease control, cardiovascular disease, things like that.”
There’s much more left to do, she said.
So what can researchers and organizations do to start revving up for the challenges of the next decade?
“In order to make progress against cancer, you’ve got to have a pipeline of investigators. And so we think about some of the young people that we’re developing at a place like [Fred Hutch] and how are we going to get the right people with the smart minds and the great idea in place and then allow them to really thrive,” she said.
On the technology side, proteomics will be an important area to invest in, she said. The field examines proteins, key agents in how our cells behave, to glean information that could be used to develop new treatments.
“And then, of course, we’re extremely excited about things that are wrapped around new therapies for cancer and we’ll be celebrating at the meeting a lot of the things that are coming along in the area of immunotherapy,” she said.
An immunotherapy treatment for a rare skin cancer called Merkel Cell Carcinoma was just approved by the FDA, making it one of just a handful of checkpoint inhibitor immunotherapies to be proven effective and safe enough for widespread use. It is the only drug approved to treat Merkel Cell Carcinoma.
The drug was developed by a team of international researchers, including Fred Hutch and University of Washington researcher Dr. Paul Nghiem, who oversaw the clinical trial that provided data the FDA needed to approve the drug.
“So to me that’s a terrific story of what we want to be able to accomplish at a center like this and then obviously what we want to be able to accomplish on a much broader scale as we think about where we’re going in cancer research across the country and across the world,” Davidson said.
Keep reading for an edited transcript of our interview with Davidson, where we touch on everything from health equity, to women’s health, to lessons that medicine could learn from tech giants like Amazon.
GeekWire: I was told you’re planning to speak about disparities and access to care, which I know is something that doesn’t get maybe talked about as much as it could. So I’m curious what you have to say on that.
Nancy Davidson: Yeah so, a couple points on that. One of them would be that my presidential theme this year — actually I wanted to think particularly about things that have to do with prevention and early detection, and then also what we call implementation science. Which is once you know something, how do you get it out into the community? So your question about health equity or disparities is one that pertains to all of those things.
From a society point of view, from the organizational point of view, I’m actually going to be overseeing a special presidential symposium at our meeting that is targeted directly towards trying to think about disparities in the United States. In this particular case, we’re thinking more nationally. So we’ll be thinking about issues that are of importance to our African-American population, to our Native Americans… and to our Hispanic population as emerging, now minorities, but soon an aggregate to be majority populations. [We’re] trying to think about the need for science that looks at cancer underlying those populations and then also thinking about… the question of implementation. How do you take what we already know and make sure that it’s widely appreciated and received by everybody across the country?
GW: So when you say cancer underlying those populations, what exactly do you mean? Do you mean ensuring that those populations are represented in cancer studies and things like that?
Davidson: We always want to make sure that in our trials patients are represented appropriately. And then I think we also want to understand whether there are any biological factors that might underlie certain kinds of cancers in certain kinds of ethnic groups. For example in my own field in breast cancer, there’s a kind of breast cancer that’s molecularly defined that’s called the triple negative breast cancer.
So these triple negative breast cancers are the ones that are not sensitive to these targeted therapies that we have currently. They’re pretty sensitive to some chemotherapies, but we’re trying to understand more about these triple negative breast cancers because they’re not especially amenable to treatment with our standard targeted therapies. Turns out that triple negative breast cancers are more common in African-American women than in women of European descent, and they’re also more common in African women, not surprisingly. And so there’s an underlying biological underpinning there that we need to understand. And then, of course, we always have… [to make] sure that they have access to the appropriate care.
GW: Let’s talk a little bit about breast cancer research, because I know that’s the area you were researching in when you were active, correct?
Davidson: I still am, I’m just not running my own lab any more. I had overseen a research lab for 30 years for Johns Hopkins and at the University of Pittsburgh, and I made the hard decision when I moved here not to have my own laboratory anymore, but to collaborate with my colleagues around here.
So my personal interest was and still remains what we call epigenetic factors and how they might have an impact on the development of breast cancer and on its treatment. And these factors are not specific only to breast cancer. They’re actually important across a variety of tumor types, and the notion is that we always think of cancers as having a multiplicity of steps of things that have to go wrong, right? And some of them are genetic changes, so they’re changes in the sequence of the DNA — mutations or translocations or loss of genetic material, and those are pretty hard to fix. It’s hard to put it back together again. But it turns out, a lot of them are what we call epigenetic changes, which are changes in the proteins that surround the DNA or subtle changes in the DNA with something called methylation, which is basically the addition of a small group of carbon and hydrogen to certain parts of the DNA.
And those changes in the proteins, called the histones, or this methylation change, can lead to differences in how a gene is transcribed, whether it’s read or not… [W]e wonder if, in some cases, these things come about because of whatever you were exposed to in the context of your life as you live it — aging, environmental factors that you might come into contact with, either external or internal. And they’re really important to me as a physician because they’re potentially reversible. And so our thought would be if these changes accumulate that they must be coming about because they promote the cancer process. But if they’re potentially reversible and we can think about how to undo them, might that be a way that we can think about combating that cancer?
And then also these methylation changes particularly are pretty easy to detect by some of the sensitive molecular techniques that we have available to us these days. PCR-based assays. And so we wonder whether or not we’d be able to use those as a way of helping people to define their risk for developing cancers at a later date. So my personal work had to do with what are the kinds of epigenetic changes we see in breast cancer systems using pre-clinical models and then whether or not we could target them with the use of epigenetic modifying drugs.
GW: OK, very cool. Do you know if the studies of those epigenetic modifiers is still ongoing?
Davidson: No, we’ve published both of them. And we’re sitting back now as a collaborative team from several centers thinking about how we want to take this forward. And we’re not the only ones. I’m interested in this in breast cancer, but this kind of work went on in parallel in colon cancer. There was an effort in lung cancer. And these drugs are actually — some of them — in routine practice now for treatment of various kinds of blood cancers because they have efficacy in certain of the leukemias.
GW: So staying on the theme of technology and therapy — I don’t know if technology would be the correct word. It always makes me think of Amazon, which is very different.
Davidson: They’re not that far apart. Amazon manages big data for a living, and that’s what we’re trying to do too, right? They are very good at it. And so I think we’re trying really hard to think a lot about the things that they’ve learned and how we can really adapt that to the field of medicine because you and I just talked about a huge amount of data. If you look at the Cancer Genomics Atlas… they have it on their website how many petabytes of data they have as a consequence of interrogating those thousands of tumors. And so trying to think about how you acquire those data, how you store them, and then how you help investigators to use them. Because of course, data by itself is not all that helpful. I need to have data that gets translated into knowledge as a practicing physician. That’s what we really need to see. So I think that Amazon and medicine, we’re not too far apart. And I think they have a skill set that we could benefit from.
GW: Very interesting. I never thought about that data comparison. It makes a lot of a sense.
Davidson: I think the other thing that they do which we need to emulate more in medicine is that they’re very customer centric. Don’t you think?
GW: Yes, definitely.
Davidson: Pretty impressive, the way that they really cater to you as a consumer and make sure that they’re wrapped around what you’re thinking and what you need as best as they possibly can. And that they’re very good at delivering. And so in a whole separate part of our lives on our Seattle Cancer Care Alliance side, I think there’s a lot that we can learn in the medical field from companies like Amazon about how to provide the best possible care for our consumers, who happen to be called patients and families.
GW: Interesting. So I’m wondering what the analog in medicine would be to something like Amazon Prime. Making things convenient and accessible, and things like that.
Davidson: We have every quarter, in the Seattle Cancer Care Alliance, we have an all-staff meeting. We had one at 8 o’clock this morning. We had one at noon to try and get everybody in. And we’re talking really intensely about those kinds of things. There are so many things that we need to do to try to up our game in terms of patient care even more. Just two to throw at you, one would be access. We heard from a patient who actually was treated here, on one of the CAR T-cell trials — Stephanie, who’s been pretty public about this, was actually the featured speaker at the dedication for the Bezos Family Immunotherapy Center a couple of months ago.
We just had her in today to talk with our staff and to remind us about how it is to be a consumer and why it is that she felt so good about the care she got in here. And one of the things I loved that she said today was she said she lives in Idaho. And when things weren’t going quite as well as she had hoped they would with regard to her Hodgkin’s disease, she said to her oncologist, “Well you know, I’ve been researching and I want to go see those people in Seattle.” He said, “Well you can’t get in to see those people in Seattle.” And she said, “Well why not?”
So she picked up the phone and she called and she got an appointment. So that’s one of the things that we want to make sure we do the way Amazon does, which is that if you pick up the phone and you want an appointment with us that we’re on that. That we try to figure out how to make that happen. So we’re doing things right now that we call Now Clinics. That if you call in and you want to be seen to talk about your newly diagnosed fill-in-the-blank, we want to be in a position where we can try to accommodate you for this consultation on your schedule almost as rapidly as you like. We probably can’t do it this afternoon, but we want to be able to do it in a relatively short period of time that’s in keeping with the anxiety that we know that you feel, which allows us to be there early on and to help you think about what evaluation is necessary, what technology do we need to bring to be able to interrogate and understand your particular cancer? And then to think with you about the best possible way to go forward with regard to your care. And of course always if there’s a possibility, we want to make sure that you’re aware of any clinical trial opportunities that might speak to you.
So there’s several parts of technology there. One of them is us, making sure that we’ve got the technology to give you that appointment right then on the phone. Then the technology that is so important now when we evaluate cancers… and then we’re going to be using these technologies as we go forward during treatment to get some sense of how the tumor’s responding.
One thing we’ve learned is that tumors evolve over time. They evolve by themselves and if you treat them they might evolve to try to circumvent the kinds of treatments that you’re bringing to bear, and so we’ve come to realize that this evolution is not uncommon, that cancers are not static. They’re quite dynamic. And we may be helped as clinicians if we’re able to follow the molecular ins and outs of that cancer because that may be able to allow us to think a little bit about whether we should be making adjustments in our treatment. And if so what kind of adjustments.
There’s a lot of interest right now in what we call liquid biopsies, which is the ability to take blood and then to be able to interrogate the shreds of DNA that are floating around in all of our blood. And this liquid biopsy technique actually was derived from the efforts that are already really coming into the mainstream to do pre-natal testing on circulating blood. I don’t know whether you follow this at all.
GW: Not particularly.
Davidson: So for women when they’re pregnant, there’s some pretty standard pre-natal testing things that can be done. In the past it’s been done by amniocentesis or by what’s called chorionic villus sampling, and both of those are invasive procedures. And so there’s been interest in whether or not you could look for some of these changes in the fetus by looking at the circulating DNA in the mom. And these techniques are pretty good, and they are beginning to do them for things like Down syndrome. You can look at those kind of chromosomal abnormalities pretty easily without having to actually go through those biopsies or those more invasive procedures.
So along the way, as this was being done, in a couple of cases they accidentally found changes that you shouldn’t see in a developing fetus and actually were reminiscent of cancer. And so that led, for a couple of these women, to evaluations where they were in fact found to have an unexpected malignancy, and that really I think propelled our field forward to think about, “Well gosh, if you can find these things accidentally, maybe we should be looking for them on purpose.” So this liquid biopsy area is very hot right now across all of oncology. And it’s especially interesting in the solid tumor world because it’s so much more difficult for us to do serial biopsies of solid tumors.
We also think it will be helpful to us because another characteristic of cancer is it’s very heterogeneous. You would think all the cells within a cancer would be exactly the same, but actually they’re quite different. It’s kind of a community in there of little micro-communities as these cells behave in slightly different ways and they have different kinds of mutations. So you can imagine that the metastasis in this part of your lung may not actually be derived from the same cell as the metastasis in that [other] part of your lung, and may not be derived from the same cell as the metastasis in your liver. And there’s no way that I’m going to biopsy all those things. But all of them have cell growth and cell death, and so that circulating DNA is going to be kind of an average. It’s going to be all of those tumors that are kicking out that DNA into your circulation and so we should be able to get a kind of more unified view of the changes in the DNA and use that to be able to think about what are the molecular changes. Do they speak to some sort of therapy resistance?
So that’s an example I think where there’s a lot of technology that’s very exciting right now and just coming into clinical investigation where we hope they’ll be opportunity to use it in clinical practice in the future.
GW: I wanted to jump back to your observation about similarities between Amazon and customer care and patient care. I think you mentioned one example being access for patients, and I think you said two examples, but then we only got to that one.
Davidson: I guess the second one I was thinking about is that I think that Amazon is at the forefront in terms of technology use and development, and I think medicine is also a place where we have a lot of interest in technology development, and we just talked about a couple areas there. And then trying to make sure when we develop those technologies that we do them in a very rigorous fashion and that we make sure when we develop them that they actually are developed to address questions that we care about. I think that one thing I want to avoid is developing a technology that doesn’t answer a question that’s important to me and that patient, and we do sometimes see those things. But the end of the day, I want to use a test or a device or an image to help me make a decision or to make a recommendation.
GW: Not just technology for technology’s sake.
Davidson: Well I think that’s absolutely right. In medicine, I think that technology has to help us to address a clinically meaningful question to that patient and to the health system and to the doctor.
GW: I wanted to touch back on antibody-based immunotherapies and checkpoint inhibitors because I think especially in the buzz we see in Seattle, there’s a strong focus on CAR T-Cell therapies. So I think we can sometimes overlook antibody-based therapies. So can you talk a little bit about Fred Hutch’s work in that area?
Davidson: One of them is that Paul Nghiem just [played a leading role in] one of the trials that basically allowed this antibody therapy for Merkel cell cancer to come into clinical practice.
I think another area that is a strength here and one that I’m just learning about as a newcomer to town, is there’s been a lot of interest in whether or not you can use antibody therapy with antibodies conjugated to other kinds of therapeutics. And so, a big effort here to think about whether or not you can attach radioisotopes of various sorts to an antibody and have that antibody recognize a specific abnormality on a cancer cell and thereby to kind of dock that radioisotope next to the cancer cell and hopefully have it spare normal cells.
So that kind of concept has been out there for a little while in cancer. In the breast cancer world again, not work done here but done in other places. The drug Herceptin or trastuzumab was the first anti-HER2 antibody and so people have used that to try to deliver chemotherapy directly to breast cancer cells. It allows you to use an anti-HER2 therapy in conjunction with the chemotherapy that by itself would be too toxic to give because it hurts the rest of the body. But because it’s linked to this antibody it really goes only to the breast cancer cells. And so that’s been a big advancement in the field of breast cancer.
Here, I think probably for almost two decades, Oliver Press and his group have been interested in whether or not you can use similar approaches in the lymphomas using a different kind of antibody. But thinking about how to use these antibodies to deliver radioisotopes to lymphoma cells. So I think that’s an area that we’re trying to think about how we can grow appropriately.
And then I would say the other critical area where we’re extremely well positioned is that as good as we think each of these things are, for things like pembrolizumab, we’re not seeing 100 percent of the patients respond. For CAR T-Cells, in some cases we’re actually seeing quite a large number of people respond, but we think that there are valid scientific reasons to think that maybe one should think about how to combine these kinds of approaches, because they tackle the immune resistance in different ways. And so we think we’re a center that’s also especially well positioned to think about how to do those combination studies in the most effective way going forward.
Another thing — the Women’s Health Initiative… For many, many years much of the work of the NIH was done in men. And actually early in my career, the woman who became the head of the NIH, Bernadine Healy, decided that we needed to do a little bit more work in women. She was a cardiologist and she realized that heart disease in women is not the same as heart disease in men. And back when she was thinking about this, this was not anybody’s thought. So Bernadine, when she was NIH director, actually led the development of the Women’s Health Initiative, and… it’s been headquartered here for many years.
So I want to put this out there because I’m somebody who’s watched it for her entire career because I do breast cancer. I’m into women’s health. I’ve watched the results of the various sub-parts of this come out over the years.
And so this [umbrella study] has been influential in a lot of things. It’s helped us to think about some of the work that has to do with risk factors for women, for things that go wrong as they age. It was the trial that led to the understanding that hormone replacement therapy, which we had all hoped was going to be great for your heart and wouldn’t have any real ill-effects, in fact turned out not be that way at all. In fact, hormone replacement therapy, if anything, jacked up your breast cancer risk a little bit and it didn’t do anything for your cardiovascular risk, and it slightly increased clots. So it itself was a study that led to the real diminution in the prescription of hormone replacement therapy for women when they reached menopause.
It’s also done a lot of work on things that have to do with diet, calcium, all sorts of stuff… this is a very large collection of women around the country followed for many, many years now. Probably a couple decades. And it has been a treasure trove of information for anybody who’s interested in all sorts of aspects of women’s health. I mean you’re in this cancer center, so you and I are talking about cancer, but it’s had just as much influence, if not more, on all aspects of women’s health. Cardiovascular risk, bone health, all these kind of things.
I think we’ve actually made a lot of headway. For example, if you look at cancer clinical trials, by and large you’re going to find that women and men are represented in the proportion where that cancer affects the population. So I think there’s a lot more science wrapped around clinical trial design then there used to be, and again, a place like this [Fred Hutch] plays a big role in it.