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Multitargeted Therapies: Promiscuous Drugs and Combination Therapies also focuses on development of novel combination therapies designed to address multiple targets. Discussed is the use of synthetic lethality to design combination therapies for cancer. We describe the use of synthetic lethal screening with RNAi to identify chemosensitizing targets for cancer therapeutics. Also described is an RNAi-based synthetic lethal screening approach to developing therapies for p53-negative cancers (p53 is a key tumor suppressor factor in the majority of human cancers).