BIM, PUMA, and the achilles' heel of oncogene addiction

Cancer cells undergo extensive genetic and epigenetic rewiring to support the malignant phenotype, and yet cell survival and proliferation often remain dependent on one or a limited number of driver mutations. This is the concept of oncogene addiction, the elucidation of which has led to substantial progress in therapeutic interventions. However, because resistance mechanisms often emerge, explicating the pathways that connect therapeutic oncogene inactivation to the cell death machinery is critical to exploiting additional synthetic lethal opportunities.