Nancy E. Davidson, MD
Associate Vice Chancellor for Cancer Research
Hillman Professor of Oncology
Distinguished Professor of Medicine and Pharmacology and Chemical Biology
Breast cancer; cancer biology; cancer policy; novel therapeutics; hormonal regulation of breast cancer growth; estrogen receptor; epigenetics
Nancy E. Davidson, MD works as a physician-scientist in the biology and treatment of breast cancer, the most common non-skin cancer in American women. Her lab was among the first to elucidate the role of apoptosis in the response of human breast cancer cells to estrogen deprivation and certain cytotoxic chemotherapies, both mainstays in the treatment of breast cancer in the clinic. This work demonstrated that these two effective therapeutics are both anti-proliferative and pro-apoptotic. Second, her team has demonstrated the feasibility of targeting the polyamine metabolic pathway in human breast cancer cells. In particular the ability of certain analogues of native polyamines to inhibit proliferation, promote apoptosis, and downregulate expression of critical molecules like the estrogen receptor (ER) protein led to the phase II testing of one such analogue in women with metastatic breast cancer. This research has truly spanned the bench to the bedside. Finally, her lab was the first to show that the ER gene (ESR1) is epigenetically regulated and that epigenetic silencing may account for the absence of ER protein expression in a fraction of human breast cancers, thereby rendering these tumors unresponsive to endocrine approaches. Her team showed that human breast cancer cell lines that lack ER expression show methylation of the CpG island in the 5' region of the gene as well as aberrant histone modification, leading to a transcriptionally inactive chromatin conformation. These changes can be reversed by exposure to DNA methyltransferase or histone deacetylase inhibitors, leading to expression of ER protein and sensitization to the growth inhibitory effects of tamoxifen. These preclinical findings are now being validated in early phase trials in women with breast cancer.