Data from Cetuximab Response of Lung Cancer–Derived EGF Receptor Mutants Is Associated with Asymmetric Dimerization
Year: 2023
Type: other
Abstract: Kinase domain mutations of the EGF receptor (EGFR) are common oncogenic events in lung adenocarcinoma. Here, we explore the dependency upon asymmetric dimerization of the kinase domain for activation of lung cancer–derived EGFR mutants. We show that whereas wild-type EGFR and the L858R mutant require dimerization for activation and oncogenic transformation, the exon 19 deletion, exon 20 insertion, and L858R/T790M EGFR mutants do not require dimerization. In addition, treatment with the monoclonal antibody, cetuximab, shrinks mouse lung tumors induced by the dimerization-dependent L858R mutant, but exerts only a modest effect on tumors driven by dimerization-independent EGFR mutants. These data imply that different EGFR mutants show differential requirements for dimerization and that disruption of dimerization may be among the antitumor mechanisms of cetuximab. Cancer Res; 73(22); 6770–9. ©2013 AACR.
Authors: Jeonghee Cho, Liang Chen, Naveen Sangji, Takafumi Okabe, Kimio Yonesaka, Joshua M. Francis, Richard J. Flavin, William Johnson, Jihyun Kwon, Soyoung Yu, Heidi Greulich, Bruce E. Johnson, Michael J. Eck, Pasi A. Jänne, Kwok-Kin Wong, Matthew Meyerson
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4392686547