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The concept of synthetic lethality in the context of anticancer therapy

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NATURE REVIEWS CANCER
Volume 5, Issue 9, Pages 689-698

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NATURE PUBLISHING GROUP
DOI: 10.1038/nrc1691

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Two genes are synthetic lethal if mutation of either alone is compatible with viability but mutation of both leads to death. So, targeting a gene that is synthetic lethal to a cancer-relevant mutation should kill only cancer cells and spare normal cells. Synthetic lethality therefore provides a conceptual framework for the development of cancer-specific cytotoxic agents. This paradigm has not been exploited in the past because there were no robust methods for systematically identifying synthetic lethal genes. This is changing as a result of the increased availability of chemical and genetic tools for perturbing gene function in somatic cells.

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