Harvard Medical School Boston, Massachusetts
Emil Frei III Professor of Medicine Director, Center for Functional Cancer Epigenetics Dana-Farber Cancer Institute
Combatting drug resistance in triple-negative breast cancer through new strategies for combination therapies.
Triple negative breast cancer (TNBC) is an aggressive subtype, and while chemotherapy and immunotherapy are successful in some patients, many develop metastasis and succumb to their disease. This is partly due to the diversity of TNBC tumors—no single therapy will be appropriate for all TNBC patients. The overarching goal of Dr. Myles Brown’s work is to discover new treatments for TNBC by further stratifying tumors into new subtypes, which can in turn reveal new therapeutic targets. For example, some TNBC tumors may be driven by the gene FGFR, which can promote growth and metastatic spread. This suggests that patients with FGFR-positive tumors could be treated with an FGFR-targeted therapy, but clinical trials have been disappointing thus far due to drug resistance.
The team is interested in learning why FGFR-positive TNBC tumors are resistant to FGFR-targeted therapy, and their work culminated in several exciting breakthroughs that were recently published in the journal, Nature Cell Biology. They discovered that high amounts of FGFR seen in some TNBC tumors alter the activity of several genes at once, reprogramming the cells in a way that cannot be treated by targeting a single gene. They further discovered that the activated genes contribute to a change in tumor cell metabolism, circumventing the cells’ dependence on FGFR, and making them resistant to FGFR-targeting therapies.
In the coming year the team will conduct molecular analysis in patient-derived tumors to confirm that their findings. In addition, they will explore the therapeutic potential of combining FGFR inhibitors with therapies that affect metabolism and the genetic reprogramming they encountered in FGFR-resistant cells.
If not for BCRF I would not have been able to explore a new area of breast cancer research and would not have discovered a potential new combination therapy for women with breast cancer. —Dr. Brown
Myles Brown, MD is Director of the Center for Functional Cancer Epigenetics at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. He obtained his BS in Biology from Yale and his MD from Johns Hopkins. Following training in internal medicine at the Brigham and Women’s Hospital, a fellowship in medical oncology at the Dana-Farber and postdoctoral research at MIT, he joined the staff of the Dana-Farber and the faculty of Harvard Medical School. Dr. Brown’s research is focused on understanding the factors underlying the hormone dependence of breast and prostate cancers. He is recognized for three seminal discoveries including the role of p160 co-activators in steroid receptor action; the dynamic nature of co-regulator function; and the predominance of steroid receptors as enhancer- rather than promoter-binding factors.
2012
The Pink Promises Award in Memory of Bonnie Karp Schwartz
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