James M. Ford, MD :: Profile
Associate Professor of Medicine
Pediatrics and Genetics
Director, Stanford Program for Clinical Cancer Genetics
Stanford University School of Medicine
The Pink Promises Award in Memory of Patricia L. Hansen
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?
I have always been interested in the sciences and biology. My parents are biologists, and I grew up doing experiments and looking at things in nature. In college I wanted to be a jazz bass player, but when that didn't work out, becoming a physician was a pretty good back-up plan!
As a student at Yale Medical School, I became very involved in cancer research in Dr. Bill Hait's laboratory, and as an oncology fellow at Stanford I focused on DNA repair with Professor Phil Hanawalt. When I started my own lab as a faculty member at Stanford, my initial studies focused on cancer genetics and cancer susceptibility, particularly in breast cancer. In the clinic, I launched our clinical cancer genetics program, one of the first on the West Coast.
Much of my lab's focus has been on how the BRCA1 and 2 genes are involved in DNA repair and the development of cancer. So, it's been really exciting for me through my career to see how our understanding of DNA repair defects in breast cancer have led to advances in the clinic. Also, our cancer genetics clinic has taken advantage of dramatically increased knowledge of the genetics of breast cancer susceptibility and new technologies to identify changes in those genes and to sequence genes in individuals. We identify and work with families with high cancer risk and try to identify those genes that are causing the risk.
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: A very exciting component of my work has been translational research: having the ability to study breast cancer in the lab, discovering fundamental aspects about the disease, and then applying that knowledge to patients in the clinic. The reverse order works, too, where my team and I look at patient information, tissue samples, and cancer biopsies that were gathered in the clinic and study them in the lab to try to learn more about the characteristics of their diseases and how we might be able to better treat or prevent them. Having the ability to take information and discoveries back and forth between the lab and the clinic will help us identify not only new therapies but also ideas for prevention or early detection of cancer.
Our projects funded by BCRF are great examples of translational research. In our earlier work, we observed that oxidative damage has an effect on the progression of breast cancer. Other studies showed that statins, which are cholesterol-lowering drugs, appear to affect the rate of oxidative DNA damage. Putting the two together, we designed a clinical trial using statins as prevention agents for individuals with BRCA mutations at high risk for breast cancer. This study, our first BCRF-funded project, is just wrapping up, and we hope to report the results soon.
Our more recent BCRF-funded project has focused on triple negative breast cancer and using PARP inhibitors as potential treatment for it. Triple negative breast cancer is of particular interest given the aggressiveness of the disease and the need for new therapies.
Right now, we are trying to identify targets within triple negative breast cancer that can be used therapeutically. Following on the exciting findings of the BCRF-funded investigator Dr. Alan Ashworth who showed that PARP inhibitors specifically target DNA repair deficient BRCA-mutant tumors, we extended this finding to the larger group of triple negative breast cancer, not solely those with hereditary BRCA 1 /2 mutations, and showed that they share a number of DNA repair defects with BRCA 1/2 mutant cell lines. They also share sensitivity to certain DNA damaging agents, including the platinum drugs, the chemotherapy drug gemcitabine, and PARP inhibitors. So, our initial work in the lab was brought to the clinic, where we are now conducting a neoadjuvant ("pre-operative") trial of a PARP inhibitor, together with gemcitabine and carboplatin, for women with triple negative breast cancer. This trial accrued very rapidly, and now we are performing a number of correlative studies in the lab to look for additional genetic changes or alterations in these tumors that might confer sensitivity or drug resistance to these combinations of drugs, and in particular to the PARP inhibitors.
As we learn more about the biology of triple negative breast cancer, we hope that additional targets with therapeutic benefit will be revealed. Determining the cause of triple negative breast cancer outside of BRCA 1/2 mutations is very important, as we need to understand better why the rates of triple negative breast cancer vary in different ethnic populations and how they may also change according to the specific environments where the individuals live.
Q: Are there specific scientific developments and/or technologies that have made your work possible? What additional advance can help to enhance your progress?
A: The major area that has affected my work and interest and will continue to do so is genomics, the study of genes and their functions at a whole genome level. These new technologies, so-called "next generation high throughput DNA sequencing," are allowing us - at a cost that's becoming much more affordable - to look at the genetic sequence in individual tumors and in individual people so that we can try to tailor, or personalize, therapy.
Being able to sequence the entire genome of individuals and individual tumors still seems inconceivable to me, but we have done it. Being able to look at a family with a very complicated family history of cancers that may not be explained by the handful of Mendelian genes we know of, like BRCA1/2, and actually being able to sequence the genome of individuals in that family and track down a genetic change that may be the susceptibility gene, is now well within in the realm of possibility. I think those are amazing advances.
Q: What direction(s)/trends do you see emerging in breast cancer research in the next 10 years?
A: Much of cancer research is moving in the direction of defining different molecular subtypes within a specific kind of cancer. For breast cancer, this discovery has brought great insights into how we think about treating the disease(s). I think the next steps are going to be identifying more targets specific to the various subtypes of breast cancer. The final extension of that, of course, would be to personalize, or understand, a cancer at the individual level, that is, sequencing all or many of the genes of a tumor and identifying a particular target of treatment that would be most effective for that patient. This is the ultimate form of personalized medicine, and the advances in genomics, as well as in developing targeted therapeutics, will bring us there.
Q: What other projects are you currently working on?
A: My lab in general is working on DNA repair processes in a number of tumors, including breast cancer. Dr. Shaveta Vinayak (2010 ASCO Young Investigator, supported by a separate BCRF grant through ASCO) is a post-doctoral oncology fellow pursuing the idea that PARP inhibitors might be used as agents for prevention of triple negative breast cancer, and has developed laboratory models to study this possibility. We also are excited about recent results from a large drug screen that identified several compounds that actually enhance DNA repair activity, and thus might serve to counteract the mutagenic consequences of unrepaired DNA damage, particularly in individuals at high susceptibility due to BRCA1/2 mutations.
Q: How close are we to preventing and curing all forms of breast cancer?
A: I think we have come a long way. Much of the work learned through BCRF-funded investigators provides convincing evidence of the major advances we have been able to make in breast and other cancers. But, of course, we have a long way to go. The technological changes and the scientific advances over the past couple of decades will really accelerate this work. As a result, there will be many new ideas for prevention and many types of cures for cancer. It's the continuum of these discoveries and their combined impact that will make a big impact in curing and preventing cancer.
Q: In your opinion, how has BCRF impacted breast cancer research?
A: BCRF has had a major impact at numerous levels. As we all know, funding for cancer research is getting harder to come by. Federal funding from the National Institutes of Health and other government resources is being cut because of fiscal difficulties. All of us are having a harder time in finding new sources of funding, so BCRF support is even more important in keeping critical projects going.
Also, the idea of gathering "the best and the brightest" around a particular problem, in this case breast cancer and its treatment and cure, has been incredibly successful. BCRF supports translational research, which is a hugely important area of research both past and future. The Foundation provides the opportunity for multiple investigators to study very deeply the basic science aspects of cancer in tandem with expert clinicians in the care of cancer and every bit in between.
In addition, the research that BCRF funds is often highly investigational and sometimes in its very earliest stages, before it can get funding or acceptance in other settings. Therefore, BCRF has been very much at the cutting edge of novel ideas, pushing research into new areas with many, many examples of success among its investigators. And, BCRF's long-term commitment to investigators, watching their scientific ideas develop and take a translational route, has been incredibly effective. This way, good ideas don't burn out too quickly but can be played out, sometimes in parallel with other ideas.
Furthermore, the general enthusiasm among the BCRF grant recipients sets this organization apart. Bringing all of us together at an annual conference creates a synergistic environment, and many interesting collaborations have come out of those meetings. I think that the enthusiasm from the leaders of BCRF is infectious to all the investigators and has had a major effect on breast cancer research in this country and internationally.
Read more about Dr. Ford's current research project funded by BCRF.