Targeting SMARCA4-deficient lung cancers

SMARCA4 alterations occur in 10% of NSCLC, are associated with poor patient outcomes, but have yet to lead to targeted therapies. SMARCA2 has emerged as a promising therapeutic target in SMARCA4-mutant lung cancers. SMARCA4 inactivation results in a dependence on SMARCA2 for cells to proliferate; thus, small molecules against SMARCA2 have been developed. Yet, the existence of highly aggressive lung cancers deficient for both SMARCA4 and SMARCA2 demonstrates that dual loss can be tolerated by proliferative cancer cells. In this project, Dr. Concepcion and her group will (1) determine the precise roles of SMARCA2 in the progression of SMARCA4-deficient lung cancers and (2) identify the molecular mechanisms that permit cells to proliferate in the absence of both SMARCA4 and SMARCA2.