The invention relates to modulating BimEL levels (Bcl-2-Interacting Mediator of cell death, Extra Long isoform) to sensitize cancer cells to cell death or apoptosis. In certain embodiments, the invention relates to increasing BimEL levels. In certain embodiments, the invention relates to inhibitors of at least one of .beta.-TrCP1/2 or RSK1/2 proteins that sensitize tumor cells to chemotherapy-induced death or apoptosis. Additionally, the invention relates to cancer therapies, diagnostics, and methods for identifying novel drugs or drug candidates for increasing BimEL levels.