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Cancer

A tumour gene's fatal flaws

Nature volume 462, pages 44–45 (2009)Cite this article

Mutations in RAS genes are common in human tumours, but RAS has proved impossible to target with drugs. Its associated NF-κB signalling pathway, however, may turn out to be this tumour gene's Achilles heel.

RAS is one of the most commonly mutated gene families in human cancers — one of its three members (KRAS, HRAS and NRAS) is mutated in about 20% of human tumours. Attempts to target mutant RAS proteins directly with small-molecule inhibitors have so far proved unsuccessful, so there has been considerable interest in finding signalling pathways that function downstream of RAS and whose blockade might be selectively toxic to tumour cells. Two papers in this issue provide evidence that targeting one such pathway, the NF-κB signalling pathway, may be an effective approach to treat RAS-mutant tumours such as lung cancers. Barbie et al.1 (page 108) identify a component of the NF-κB pathway as a potential target in RAS-mutant cancer cells, and Meylan et al.2 (page 104) show that inhibition of NF-κB signalling impairs tumour formation in a mouse model of RAS-induced lung cancer.

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Figure 1: The RAS and NF-κB signalling pathways.

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  1. Julian Downward is at Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. downward@cancer.org.uk ,

    Julian Downward

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Downward, J. A tumour gene's fatal flaws. Nature 462, 44–45 (2009). https://doi.org/10.1038/462044a

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