Nancy E. Davidson, MD :: Profile
Director, University of Pittsburgh Cancer Institute and UPMC Cancer Centers
Associate Vice Chancellor for Cancer Research
Hillman Professor of Oncology
Professor of Medicine and Pharmacology & Chemical Biology
University of Pittsburgh School of Medicine
Member, BCRF Scientific Advisory Board
Q: Tell us about yourself as a scientist and how you became interested in breast cancer research. Did you ever seriously consider another kind of career than that of the sciences?
A: Since high school, I've been very interested in biology. Because of a weekend program at the National Naval Medical Center I decided that I wanted to study it in college. Then, I had the chance to work in a liver cancer research lab as an undergraduate, so that brought me into the field of cancer. Because of that job and through a happy series of coincidences, after my first year at Harvard Medical School I found myself at a summer job at the National Cancer Institute with Drs. Marc Lippman (University of Miami) and Kent Osborne (Baylor College of Medicine), two other people who have been really helped by BCRF support. They were very interested in things that might make these breast cancer cells grow in the laboratory, such as estrogen and peptide growth factors, so at the time they were studying a lot of the signaling pathways that we now target when we treat women with breast cancer.
That summer job made me absolutely fall in love with breast cancer. The connection between the science and the potential clinical implications made me decide that I wanted to be a breast cancer researcher, which then dictated how I developed the rest of my medical career. After my internal medicine training at Harvard, I went back to work with Dr. Lippman to specialize in medical oncology, especially breast cancer. This is a wonderful example of how you know you have some idea of what you want to do, but then over time things fall into place, you have great opportunities and you are really influenced by visionary people like Marc and Kent.
Q: Briefly describe your BCRF-funded research project. What are some laboratory and/or clinical experiences that inspired your work? What are your primary goals for this research?
A: I've been funded by BCRF for 13 years in several different capacities, each very different but equally important in terms of the impact on our field - as an independent investigator; as a co-founder of the Translational Breast Cancer Research Consortium (TBCRC), a consortium of investigators across North America/United States; and as an investigator as part of an international collaboration.
As an independent investigator, my laboratory's project has changed over time as science has changed over time. Most recently, we have focused on epigenetics in breast cancer. The concept here is that all cancers, including breast cancer, come about because of an accumulation of changes. Many of those are genetic changes, changes in the DNA sequence, but some of them are what we call epigenetic changes, which come about either because of a little tag called a methyl group that can be put on the DNA that might change the way it behaves or because of changes in proteins that are associated with DNA called the histones. And the important thing about these epigenetic changes is that they are potentially reversible whereas genetic ones are not.
It turns out that these epigenetic changes can change either the methyl group or the histone proteins in a way that DNA is not transcribed, or it's not read, in the way that it normally should be. We think some of these blocks might actually contribute to the process of developing a disease like breast cancer. And so we wonder if we could reverse these blocks, might we be able to have the cancer cells revert to a more normal type of behavior? There are already drugs that can reverse these changes, called methyltransferase inhibitors and histone deacetylase inhibitors. In the laboratory, we've looked at these drugs, individually and then in combination, and we've been able to show that using these drugs leads to a decrease in breast cancer cell growth in the laboratory. This also leads to a change in the gene expression patterns in the laboratory, and we wonder whether or not the change in DNA methylation and conformation and gene expression patterns might lead to a more favorable kind of profile that would lend itself to halting growth of the tumor or perhaps even tumor death.
We also wonder whether these kinds of drugs can make tumor cells more susceptible to other kinds of drugs, such as tamoxifen or aromatase inhibitors. Extending our work through the Translational Breast Cancer Research Consortium, whose studies are partially funded by BCRF, my colleague Dr. Vered Stearns (Johns Hopkins University) just finished a trial on that concept, looking at women with breast cancer where half of them take routine neoadjuvant (pre-operative) chemotherapy and the other half take chemotherapy with one of these epigenetic-modifying drugs to see whether or not it would enhance the effects of chemotherapy. Epigenetics is an area that has really gone from the bench to the bedside and now we're taking some of these bedside observations back to the bench again.
Another area where we are grateful to BCRF is the investment that they've made to forge interactions around the world. For eight years, BCRF has been funding a collaboration between the North American Breast Cancer Group, which is comprised of leaders of the National Cancer Institute (NCI) clinical trials cooperative groups across North America, along with leaders in the Breast International Group, comprised of leaders across the globe, to allow us to think about things that are important to all of us as investigators. So far the group has been very influential in putting out some major guidelines, such as how to measure Ki-67, which is an increasingly important biomarker for breast cancer. We needed to have some international perspective about the best way to measure such a test. We also presented results of that study at the 2012 San Antonio Breast Cancer Symposium.
Q: Are there specific scientific developments and/or technologies that have made your work possible? What additional advancements can help to enhance your progress?
A: Our BCRF funding has allowed us to work to put epigenetics on the map as an important component of the breast cancer process, and that would not have been so easy to do without BCRF. This is an area that was slower to take hold than some others. Working to understand some of these mechanisms in epigenetics ourselves and to share this work so that others can see this information as well has been important. And I think this recognition of the importance of epigenetics has become much broader across breast cancer as a consequence of the work we've been able to do and the investment that BCRF has made in helping us to do that work.
Q: What direction(s)/trends do you see emerging in breast cancer research in the next 10 years?
A: When I look at what we've accomplished over the last decade, in terms of trying to reduce the burden of breast cancer, I think that we've made enormous progress in trying to "right size" therapy, prevention, and detection. We've been trying to provide care that is the most appropriate for each individual woman and her particular kind of cancer. And I think we've done a nice job at trying to limit therapy, to try to make sure that we do just enough but not too much. And so I think that our progress over the next decade is going to continue along these lines, whether you want to call it personalized cancer care, precision care, or individualized care. We're going to be able to learn about the cancer and the individual, both from a biological perspective but also from a psychological perspective, as you need to know what makes that person tick to be able to provide her with the best possible counsel for what she needs to do.
Also, though it's a very challenging area, I hope that we will see ever more attention to prevention strategies. We'll be able to think even more about the kind of lifestyle changes or the lifestyles that people need to pursue. And I hope that we will be able to utilize the information that we already have about using prevention strategies, drugs like tamoxifen or raloxifene, appropriately.
In addition, I hope that we're going to be able to do ever less surgery for women. I hope that we're going to be able to be very, very tailored about how we think about our drug therapy and that we're going to be in a position where we can try to limit both under-treatment and over-treatment as much as possible. And I surely hope that we're going to be able to make more headway in the field of metastatic breast cancer than we've been able to do, both in terms of trying to prevent it from happening and having better therapies if it does develop. These are all areas that I'm really excited about.
Q: What other projects are you currently working on?
A: One of the enormous pleasures for me from the perspective of a cancer center director, has been to be able to take a larger leadership role in the cancer community. For the last several years, I've been the director of one of the nation's 41 comprehensive cancer centers. That means a lot of the projects that I'm doing are, of course, related to cancer more generally. One of the reasons why I think that I've been able to do that is because so many of the things we've learned to do in breast cancer are now coming true across all of oncology, so that connections between the pathways and the science and medicine are really permeating throughout oncology. I'm very excited about those projects.
When I came to the University of Pittsburgh, the generosity of BCRF allowed me to found our Women's Cancer Research Center, which is a group of investigators heavily focused on women's cancers. Support from BCRF allowed us to recruit additional scientists, one of whom is Dr. Steffi Oesterreich, who is now a BCRF investigator in her own right with a particular focus on the biology of invasive lobular cancer.
Q: In your opinion, how has BCRF impacted breast cancer research?
A: What I love about BCRF funding is that it's allowed me to pursue an area that I think is really important but was viewed as a little bit "out there." BCRF grants have allowed us to do the work that eventually led to more traditional funding mechanisms and then ultimately impact clinical practice. For example, when I was at Johns Hopkins, our SPORE grant at the time had a project that was the clinical spin-off of how to take some of these epigenetics treatments and actually put them into clinical trials - this clinical application through the SPORE was made possible by foundational support from BCRF for the preclinical science.
These funds have also allowed me along the way, at times when I thought it was important to make a critical strategic investment in somebody else's work, to make a big difference so their work could go forward. Here at Pitt, I had the chance, for example, to help support a young investigator who is really interested in DNA repair and why it is that cancer cells don't repair themselves in the way that they should and how it is we can actually take advantage of that defective repair - how it might be an Achilles heel for some cancers. I was able to use BCRF funding to help to support his work at a key moment in his work to allow him to move his work forward and obtain funding from the National Institutes of Health.
The other fabulous thing about BCRF is that the organization has been really open to innovative partnerships. In 2005, many of us breast cancer investigators in SPORE initiatives wanted to be able to band together more routinely and work together over long periods of time. So that led to the founding of the Translational Breast Cancer Research Consortium. BCRF provided the pivotal gift to launch that particular organization, and it's been a very successful unification of now 17 different cancer centers around the country. TBCRC has allowed us to try to do small, very scientifically-driven, often very resource- and specimen-intense clinical trials across the members of our consortium. Our first trials are now in press in the breast cancer literature. We've had several well-received presentations at the Annual Meeting of the American Society of Clinical Oncology (ASCO) and at other big international meetings over a short period of time.
Also, I want to put on my hat as former ASCO president for a moment and talk about what an unbelievably great partner BCRF has been for ASCO. I am, personally, incredibly grateful for the support that BCRF has given to several ASCO career development activities, including the Young Investigator Award, the Career Development Award (CDA), and the Advanced Clinical Research Award. Currently, I work with Dr. Shannon Puhalla, who is using her BCRF-funded CDA grant to develop her credentials and experience as a clinical investigator. At Johns Hopkins, I worked with Dr. Vered Stearns, who was the first Advanced Clinical Research Award winner in breast cancer supported by BCRF. The ways that BCRF connects the oncology field for me are very, very palpable. I see how BCRF has touched our field. I see how it's touched individuals, and I know how grateful everybody is for the support that BCRF provides - both financial support and networking support. We owe so much to Evelyn Lauder for her vision for BCRF and what it has accomplished and will continue to do.
Read more about Dr. Davidson's current research project funded by BCRF.