Myles Brown, MD
Emil Frei III Professor of Medicine
Director, Center for Functional Cancer Epigenetics
Dana-Farber Cancer Institute
Harvard Medical School
Combating 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.
Dr. Brown’s team discovered what drives FGFR-therapy resistance in TNBC tumor cells: 1) they alter the activity of several genes at once, 2) the activated genes all contribute to a change in metabolism within the tumor cells, and 3) the altered metabolism activates another molecule, circumventing the cells’ dependence on FGFR. In a laboratory study, Dr. Brown and team found that using drugs which target either the first step (wherein several genes are activated at once), or the third step (the molecule that circumvents FGFR dependence), successfully overcame resistance to FGFR therapy.
In the coming year Dr. Brown’s team will continue to validate these findings in the lab. This includes testing multiple combinations of potential drugs that could work together with FGFR inhibitors, as well as exploring other mechanisms of resistance in FGFR-positive cells—tumors often harbor several ways of evading therapies. The team will also test if their discoveries in FGFR resistance could be applicable to similar drugs, like inhibitors for the molecules EGFR and PDGFR. If cancer cells develop resistance to these drugs in the same way, the combination therapies they design for FGFR may work for EGFR and PDGFR therapies as well.
Dr. Myles Brown 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.
The Pink Promises Award in Memory of Bonnie Karp Schwartz
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