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Semin Oncol. 2006 Aug;33(4):513-20.

Targeting loss-of-function mutations in tumor-suppressor genes as a strategy for development of cancer therapeutic agents.

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  • 1The Translational Genomics Research Institute, Translational Drug Development Division, Phoenix, AZ 85004, USA. hwang@tgen.org


Two types of genetic mutations, gain-of-function in oncogenes and loss-of-function in tumor-suppressor genes, are important molecular bases of tumorigenesis of human cancers. Target-based drug discovery is the main stream of contemporary cancer therapeutic development but largely focuses on gain-of-function mutations in oncogenes. Loss-of-function mutations in tumor-suppressor genes are often neglected as therapeutic targets. In this review, we discuss the feasibility of targeting loss-of-function mutations in tumor-suppressor genes for the identification of cancer-specific therapeutic agents.

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