Dana-Farber Cancer Institute
Professor, Biological Chemistry & Molecular Pharmacology
Harvard Medical School
Professor, Cancer Biology, Dana-Farber Cancer Institute
Co-leader, Breast Cancer Program, Dana-Farber/Harvard Cancer Center
Developing safe and effective therapeutic strategies for treating BRCA1-deficient triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is an aggressive form of the disease with poor prognoses and limited treatment options. PARP inhibitors have emerged as an effective treatment for TNBC tumors that are deficient in DNA damage repair (due to defective BRCA1). However, the impact of PARP inhibitors in patients with advanced BRCA-associated TNBC is relatively modest. Dr. Zhao and her colleagues are investigating how the establishment of an immune suppressive tumor microenvironment promotes resistance to PARP-inhibitors and evaluating strategies to overcome this resistance. Her research will inform the development of more effective therapies which will benefit more patients with this aggressive form of breast cancer.
Dr. Zhao and her team have developed and characterized several laboratory models of invasive TNBC that is driven in part by the loss of the BRCA1 gene. Using these models, they discovered an important mechanism of drug resistance that is mediated by macrophages – a type of immune cell – present in BRCA-deficient breast tumors. Their recent findings include understanding deep mechanistic details of how major cancer driving genetic alterations, such as BRCA1 and PTEN mutations, protect both tumor cells and tumor-associated immune cells from anti-tumor immunity and promote tumor progression.
In the coming year, the team will use their state-of-the-art TNBC laboratory models to develop effective combination treatments to improve outcomes for patients with breast cancer. Their results will facilitate translation of pre-clinical studies into tangible benefits for patients with advanced breast cancer harboring key genetic mutations who currently have limited treatment options.
Jean Zhao is Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and Dana-Farber Cancer Institute (DFCI). Dr. Zhao’s research focuses on understanding kinase signaling pathways in cancer. She is a pioneer in understanding signal transduction by integrating genetics and pharmacological approaches, thus changing the way we think about important problems in the targeted therapy of cancer. Specifically, she has conducted seminal work to determine distinct roles of isoforms of PI3K in the normal physiological functions and in the pathogenesis of cancer. Her work laid a foundation for the new field of targeting isoforms of PI3K in cancer and guided the design of current clinical trials of PI3K inhibitors for cancer patients. Dr. Zhao is a leader in the systems and functional approaches to targeting kinases in cancer and has identified several novel oncogenic kinases and lead compounds, providing the groundwork for innovative therapeutic interventions. More recently, she is leading a major effort to establish patient-derived models of metastatic breast cancer. This work is designed to investigate the molecular and genetic basis for this disease and the mechanisms of drug resistance to translate fundamental preclinical findings into novel and improved therapeutic strategies for patients. Dr. Zhao’s honors and awards include Career Development Awards from NIH/NCI, V Scholar Award and Starr Foundation Award. She is a member of Committee for Women Faculty and Executive Committee for Research at DFCI and serves as Co-Leader of the Breast Cancer Program at Dana-Farber/Harvard Cancer Center.
BCRF support will allow us to tackle challenging yet rewarding studies in BRCA1-mutant and PTEN-deficient triple negative breast cancer.
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