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A COLLABORATORY FOR CANCER RESEARCH

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NCI / FNL Workshop on RAS Synthetic Lethality

By James Hartley

Frederick National labs

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Abstract

"Synthetic lethality" is a term of classical genetics that refers to a combination of defective genes that is deadly together (synthetically, i.e., when both genes A and B are inactivated) but not when one or the other (A or B) is inactive. It is known that animal models of cancer can be completely dependent on expression of oncogenic RAS genes (DePinho et al., Nature 400, 468, 1999; Varmus et al., Genes Dev. 15, 3249, 2001), and it is also known that some human cancer cell lines die when RAS genes are inhibited (for example, using RNAi). Several large (but probably not large enough; see below) synthetic lethal screens have been done to find genes that, when inhibited with RNAi, cause cells that express mutant KRAS to die, while not affecting cells expressing wild type KRAS. However, the hits from those screens did not converge on a common set of targets.

The NCI and FNL organized a workshop in January, 2014, at the RAS Hub in Frederick Maryland. Here the results of the workshop are summarized.

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