The mechanistic and therapeutic implications are twofold: (1) BCL-xL is a primary anti-apoptotic barrier in TIS cancer cells, and HRK downregulation is a molecular driver that can be targeted to eliminate TIS cancer cells; and (2) strategies that prevent HRK loss or disrupt the BCL-xL-BAK interaction directly may enhance the efficacy of senolytics against TIS cancer cells. This evidence concerns the gene BCL2L1 and cancer.