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by Leigh MacMillan | Posted on Thursday, Oct. 10, 2013 — 8:00 AM
Mutations in the epidermal growth factor receptor (EGFR) are found in many lung cancers. Certain EGFR mutants render tumors sensitive to the targeted therapies gefitinib and erlotinib, but the tumors eventually acquire resistance.
William Pao, M.D., Ph.D., Monica Red Brewer, Ph.D., and colleagues used biochemical and structural studies to determine whether mutant EGFRs in lung cancer adhere to the established mechanism for EGFR activation. This mechanism involves an asymmetric interaction between two receptor molecules, with a “donor” contacting – and activating – an “acceptor.” The investigators found that mutated EGFRs do use asymmetric dimerization, but that the oncogenic mutant receptors preferentially assume the “acceptor” role when co-expressed with wild-type EGFR. This “super-acceptor” activity leads to hyperphosphorylation and activation of wild-type EGFR, and also the related ErbB-2 family member.
The findings, reported Sept. 17 in the Proceedings of the National Academy of Sciences, have implications for understanding mechanisms of drug sensitivity and resistance in EGFR mutant lung cancers, which could be exploited for therapeutic benefit.
Leigh MacMillan, (615) 322-4747
Health and Medicine, Reporter, Research Aliquots, Department of Medicine, division of hematology/oncology, EGF, EGFR, Epidermal growth factor, lung cancer, NCI, NIH, personalized cancer medicine, PNAS, Reporter Oct 11 2013, V Foundation, Vanderbilt Ingram Cancer Center, William Pao
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