Research ArticleCancer

Afatinib restrains K-RAS–driven lung tumorigenesis

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Science Translational Medicine  20 Jun 2018:
Vol. 10, Issue 446, eaao2301
DOI: 10.1126/scitranslmed.aao2301

A new role for kinase inhibitors

The K-RAS oncogene is frequently mutated in a variety of cancer types, including lung cancer. Lung cancers with K-RAS mutations are usually difficult to target, and conventional thinking dictates that these tumors are resistant to receptor tyrosine kinase inhibitors because those act upstream of the constitutively active K-RAS protein. However, it appears that receptor tyrosine kinase signaling may have an effect on K-RAS–driven lung tumors after all, by amplifying their growth beyond the effects of K-RAS alone. Kruspig et al. and Moll et al. independently reached this conclusion and identified approved multikinase inhibitors that are effective in the setting of K-RAS–mutant lung cancer in multiple mouse models, suggesting that this may be a potential treatment strategy for human patients as well.

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