Dana-Farber Cancer Institute Boston, Massachusetts
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 driven by mutations in the BRCA1 gene mutation. However, the impact of PARP inhibitors in patients with advanced BRCA-associated TNBC is relatively modest. Dr. Zhao and her colleagues are investigating how 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 discovered that BRCA1-mutant breast cancer cells can hijack immune cells called macrophages to support tumor growth. They found that this effect can be blocked by stimulating a factor called STING that reprograms these macrophages to attack tumors. Dr. Zhao and her team have tested this concept in laboratory models of invasive TNBC that are driven in part by the loss of the BRCA1 gene. They found that stimulating STING in these models reduced tumor formation and increased tumor-fighting macrophages.
In the coming year, the team will continue their efforts to understand the complex interplay between cancer cells and the immune system. They will use their state-of-the-art models to determine if reprogramming macrophages can prevent the initiation and progression of tumors. They are also interested in how a protein called PI3Kβ contributes to the development of tumors in laboratory models. Their results will provide the key knowledge needed to create additional treatment options for patients with advanced breast cancer harboring key genetic mutations.
“Without the support of BCRF, we would not have been able to uncover these groundbreaking insights into the novel molecular and cellular mechanisms that govern the tumor and its immune microenvironment. These discoveries are pivotal in paving the way for the development of safer and more efficacious treatment strategies for patients with breast cancer.”
Jean J. Zhao, PhD 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 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.
2015
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