Targeting BRD9 in Sarcoma

Background
Synovial sarcoma is a well-recognized form of soft-tissue sarcoma that occurs in children and young adults. Unfortunately, most synovial sarcoma patients ultimately succumb to the disease, largely due to a lack of effective treatment options. This highlights the need to develop new treatments to improve the outlook for people diagnosed with this disease. The work in our laboratory is focused on understanding the mechanisms that make cancer cells different from normal cells. We are designing new ways to target and eliminate cancer cells, providing improved options for the treatment of cancer patients. Our recent work identified a protein named BRD9 which is essential for the survival of synovial sarcoma cells, suggesting that targeting BRD9 may provide a new therapeutic approach. 

Project Goal
Therefore, we developed new drug compounds capable of blocking BRD9 function in synovial sarcoma cells. Our current work is focused on a better understanding of the role of BRD9 and testing the effectiveness of these new drug-like compounds in synovial sarcoma model systems. This work will be essential as this is a potential new therapeutic approach to be used in the clinic with patients.

We are also seeking to identify additional drug targets in synovial sarcoma cells and design new drug compounds to further expand potential treatment options. We expect this work will significantly expand our understanding of synovial sarcoma, potentially advance the types of treatments available to synovial sarcoma patients and ultimately improve the survival rates for these patients.

Project Update - June 2020
Chromosomal rearrangements are a common type of mutation found in pediatric cancers. These rearrangements often produce abnormal proteins called fusion-proteins that are central for pediatric cancer development and survival. This commonly happens in a pediatric and young-adult cancer called synovial sarcoma. In our studies, we have identified a new protein, BRD9, that is critical for the function of this tumor causing fusion-protein. We have developed chemicals that lead to degradation of the BRD9 protein. Remarkably, these chemicals stop the proliferation of synovial sarcoma cells in the lab and in animals but don't have effects on other cell types. We are now screening for combination approaches that might lead to even further efficacy with the goal of these approaches making it to clinical assessment.