The primary focus for targeted cancer agents has typically been to counteract the oncogenic signaling that results from genetic defects. A new strategy is emerging that actually seeks to exploit the oncogenic features of tumor cells rather than overcome them. Synthetic lethality (SL) is a situation in which 2 nonlethal mutations become lethal to a cell when they are present simultaneously. If SL were to be exploited for anticancer therapy, it could lead to the development of highly selective, less toxic drugs, while expanding therapeutic targets to include those that have, until now, proven pharmaceutically intractable. Here, we discuss the idea of SL and how it can be applied to cancer therapy.
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