A Curious Link Between Epidermal Growth Factor Receptor Amplification and Survival: Effect of “Allele Dilution” on Gefitinib Sensitivity?

Open Access
Publisher Website
Google Scholar
Abstract
The past few months have seen an increasing number of publications that confirm and extend the discovery in 2004 that specific epidermal growth factor receptor (EGFR) mutations in lung tumors are linked with clinical responsiveness to gefitinib and erlotinib ( 1 – 3 ) . These emerging data are especially exciting, because the genetic, biological, and clinical implications directly interrelate with each other to provide new directions for basic research and new optimism for the management of the major cause of cancer deaths worldwide. Clinicians, however, have to temper their enthusiasm because only a minority of patients may benefit from treatment and there is still uncertainty in how to best select these patients. For example, although EGFR mutational status was the best predictor for overall survival in two recent series of gefitinib-treated lung cancer patients from Japan ( P = .0053) ( 4 ) and Korea ( P <.001) ( 5 ) , these and other studies ( 1 , 3 ) have shown that objective responses can occur in tumor samples containing an apparently wild-type EGFR sequence and, conversely, tumors carrying EGFR mutations eventually develop resistant disease ( 6 , 7 ) . In addition, prolonged survival and clinically meaningful improvements in symptoms may be detected in selected patients with stable disease ( 8 , 9 ) that may not be as tightly associated with the presence of specific EGFR kinase domain mutations.

This publication has 31 references indexed in Scilit: