Therapeutically targeting aberrant chromatin remodeling in sarcomas

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Charles W. M. Roberts, M.D., Ph.D.,  Dana-Farber Cancer Institute
Recipient of the: $25,000 research award, Michael Mandell/Run for a Sarcoma Cure Research Award

SNF5, a core subunit of the SWI/SNF chromatin remodeling complex, is a potent tumor suppressor that is specifically mutated in several types of sarcoma.  It has been thought that oncogenesis in the absence of SNF5 occurs due to a loss of function of the SWI/SNF complex.  However, based upon preliminary data we hypothesize that cancer instead arises due to oncogenic activation of the residual SWI/SNF complex.  We propose to utilize our genetically engineered mouse models to demonstrate this, to further establish that targeted inhibition of residual activity can be therapeutically beneficial, and to establish a pre-clinical model.