Nancy E. Davidson, MD

2012-2013 BCRF Projects:
1) (made possible by the BCRF Board of Directors and Advisory Board)
Breast cancer develops as a consequence of cumulative genetic and epigenetic changes. Dr. Davidson's lab has focused on the potential therapeutic approach of reversing epigenetic changes, particularly the possibility of altering the activity of two types of histone-modifying enzymes. Their work suggests that orchestrated interplay between LSD1 and certain HDACs leads to fundamental epigenetic changes, especially in triple negative human breast cancer cells. Dr. Davidson and colleagues postulate that combining therapies targeting crosstalk between these two critical histone modification systems may represent a new and effective approach to curb the growth of breast cancer, especially the aggressive triple negative subtype. This project is clinically relevant as Dr. Davidson and colleagues will explore the unknown mechanisms underlying the crosstalk between two critical chromatin modifiers and advance a novel approach of reprogramming the epigenetic changes that could lead to the development of novel more effective combination strategies in triple negative breast cancer therapy, as it is unlikely that monotherapy will suffice.

Mid-year Progress: Dr. Davidson's work has focused on the ability to identify and target epigenetic abnormalities because they are potentially reversible. Epigenetic abnormalities can include changes in DNA methylation and alterations to the histone proteins that are closely associated with DNA--together these changes can regulate the ability of DNA to be translated into mRNA and functional proteins. Multiple families of enzymes play a role in epigenetic gene regulation. Dr. Davidson's current focus is on the role of the DNA methyltransferases, histone deacetylases, and lysine demethylases because potential agents that can target these enzymes are available. Over the last six months, her laboratory has explored the tight interplay between histone deacetylase and histone demethylase activities using inhibitors in human breast cancer cell line models. These studies have shown synergistic growth inhibition, particularly of triple negative breast cancer cell lines, and ongoing work is unraveling the mechanisms for these growth inhibitory effects in the hope that this approach can ultimately be translated into human trials.

2) On behalf of North American Breast Cancer Group (NABCG) and the Breast International Group (BIG)

The goal of the collaborative effort between the Breast International Group (BIG) and North American Breast Cancer Group (NABCG) is to reduce the burden of breast cancer through promotion of joint research efforts around the world. Investigators meet annually in the US or Europe to chart research directions and organize their activities through several working groups ranging from bioinformatics to treatment of metastatic breast cancer to survivorship. The theme for the 2012 meeting in Brussels, Belgium, was "triple negative" breast cancer, and the tentative theme for the 2013 meeting in Washington, DC, is on "next generation sequencing" technologies for breast cancer in the context of biomarkers for clinical trials. Thanks to BCRF support, members of the BIG/NABCG have published influential position papers in four areas over the last year: standards for uniform collection of biospecimens from neoadjuvant breast cancer clinical trials, measurement of Ki67, standard definitions and endpoints in neoadjuvant breast cancer clinical trials, and pregnancy after breast cancer.

Mid-year Progress: Follow-up from the 2012 meeting in Brussels, Belgium on triple negative breast cancer continues. The theme for the 2013 meeting in Washington DC has been modified to focus specifically on opportunities for international collaborative research utilizing "next generation sequencing" to investigate metastatic breast cancer. A task force is hard at work reducing this concept to an efficient and pragmatic study design.

Bio:
Nancy E. Davidson, MD, serves as Director of the University of Pittsburgh Cancer Institute and UPMC Cancer Centers and associate vice chancellor for cancer research at the University of Pittsburgh. She is responsible for all aspects of cancer research, care, and education within the University of Pittsburgh and UPMC health system. She holds appointments as Professor of Medicine, Pharmacology and Chemical Biology, and the Clinical and Translational Science Institute at the University of Pittsburgh School of Medicine.

Dr. Davidson is internationally known for her research in breast cancer. Her laboratory research has focused on epigenetics and breast cancer. She has been a leader in the conduct of breast cancer clinical trials in the national setting, previously serving as chair of the Eastern Cooperative Oncology Group's Breast Committee. She is author of over 200 scholarly papers and has been continuously funded by the National Institutes of Health since 1989.

Dr. Davidson received her bachelor's degree from Wellesley College and medical degree from Harvard Medical School. She completed internal medicine training at the University of Pennsylvania and Johns Hopkins and a medical oncology fellowship at the National Cancer Institute. She spent 23 years on the faculty at Johns Hopkins, serving as Professor of Oncology and Biochemistry and Molecular Biology and director of the Breast Cancer Program at the Johns Hopkins Sidney Kimmel Cancer Center.

Dr. Davidson was president of the American Society of Clinical Oncology in 2007-8 and has been an elected member of the Boards of Directors for the American Association for Cancer Research, American Society of Clinical Oncology, and Association of American Cancer Institutes. She serves on the external advisory boards for eight National Cancer Institute-designated cancer centers and is a member of the scientific advisory boards for the V Foundation for Cancer Research, Sidney Kimmel Foundation for Cancer Research, and the Breast Cancer Research Foundation. Among her many honors are the Brinker International Award for Breast Cancer Research, AACR-Women in Cancer Research Charlotte Friend Award, National Cancer Institute Rosalind E. Franklin Award, and American Society of Clinical Oncology Gianni Bonadonna Breast Cancer Award.