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FEBS Lett. 2010 Jun 18;584(12):2699-706. doi: 10.1016/j.febslet.2010.04.019. Epub 2010 Apr 11.

Oncogenic mutant forms of EGFR: lessons in signal transduction and targets for cancer therapy.

Author information

1
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.

Abstract

The EGF-receptor is frequently mutated in a large variety of tumors. Here we review the most frequent mutations and conclude that they commonly enhance the intrinsic tyrosine kinase activity, or they represent loss-of-function of suppressive regulatory domains. Interestingly, the constitutive activity of mutant receptors translates to downstream pathways, which are subtly different from those stimulated by the wild-type receptor. Cancer drugs intercepting EGFR signaling have already entered clinical application. Both kinase inhibitors specific to EGFR, and monoclonal antibodies to the receptor are described, along with experimental approaches targeting the HSP90 chaperone. Deeper understanding of signaling pathways downstream to mutant receptors will likely improve the outcome of current EGFR-targeted therapies, as well as help develop new drugs and combinations.

PMID:
20388509
PMCID:
PMC2892754
DOI:
10.1016/j.febslet.2010.04.019
[Indexed for MEDLINE]
Free PMC Article

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