A genome-wide CRISPR screen in SMARCA4 mutant lung cancer cell lines demonstrated that loss of MCL1 can sensitize SMARCA4 mutant lung cancer cells to SMARCA2 degradation and that the SMARCA2 degrader PRT3789 coupled with the MCL1 inhibitor PRT1419 synergistically interacts with and does not affect SMARCA4 mutant lung cancer models. Here, SMARCA4 is linked to lung cancer.