Understanding the mechanisms underpinning therapeutic vulnerability of SWI/SNF deficient cancers

SWI/SNF chromatin remodelling complexes regulate gene expression, DNA repair, replication stress responses and chromosome segregation. SWI/SNF genes are mutated in a striking number of cancers, which provides therapeutic opportunities. By identifying synthetic lethal relationships, or genes required for viability in SWI/SNF deficient cells, we can selectively target the cancer. Inhibitors targeting several known synthetic lethal relationships are in clinical use. However, responses are variable, and it is not clear why some SWI/SNF deficient cells are vulnerable, yet others are not. In this project, we will mechanistically explore these vulnerabilities to understand the contexts in which inhibitors are most effective.