Sheng Sun, PhD
Massachusetts General Hospital Cancer Center
The majority of breast cancers express hormone receptors, and therapies that antagonize hormonal signaling via these receptors are the most effective treatments for hormone receptor-positive metastatic breast cancer (HR+ MBC). Unfortunately, for the vast majority of patients with hormonal therapy-refractory MBC, the mechanisms of resistance remain poorly understood. Thus, identifying new mechanisms of hormonal therapy resistance and understanding how to overcome them will have direct and immediate relevance to the therapy of patients with MBC. We have identified novel gene fusions in 14% of patients with HR+ MBC and provided strong evidence that these tumor-specific genetic rearrangements are powerful drivers of treatment resistance and poor outcomes. Successfully tracking and therapeutically targeting these fusions could thus have a major impact on patient outcomes. We hypothesize that patient-derived circulating exosomes (tiny cell-derived vesicles that circulate in the bloodstream) are likely to contain unique nucleic acids and proteins corresponding to the fusions that could potentially serve as novel biomarkers.
We propose to credential these patient-specific rearrangements as blood-based markers of disease burden, clinical response and treatment outcome in MBC. This work will pave the way for effective disease monitoring that will facilitate the clinical development of targeted therapeutics to overcome treatment resistance mediated by these genetic drivers.
Dr. Sheng Sun obtained his Ph.D. in Biomedical Sciences at The University of Texas MD Anderson Cancer Center. During his doctoral studies, Dr. Sun investigated the function and regulation of ESCRTs (Endosomal Sorting Complex Required for Transport), the protein complexes involved in endosomal sorting and exosome biogenesis. Dr. Sun is currently a postdoctoral research fellow at the Massachusetts General Hospital Cancer Center/Harvard Medical School in the laboratory of Dr. Leif W. Ellisen.