title: Pharmacogenomics of EGFR-targeted therapies in non-small cell lung cancer: EGFR and beyond.
abstract: Commonly observed aberrations in epidermal growth factor receptor (EGFR) signaling have led to the development of EGFR-targeted therapies for various cancers, including non-small cell lung cancer (NSCLC). EGFR mutations and overexpression have further been shown to modulate sensitivity to these EGFR-targeted therapies in NSCLC and several other types of cancers. However, it is clear that mutations and/or genetic variations in EGFR alone cannot explain all of the variability in the responses of patients with NSCLC to EGFR-targeted therapies. For instance, in addition to EGFR genotype, genetic variations in other members of the signaling pathway downstream of EGFR or variations in parallel receptor tyrosine kinase (RTK) pathways are now recognized to have a significant impact on the efficacy of certain EGFR-targeted therapies. In this review, we highlight the mutations and genetic variations in such genes downstream of EGFR and in parallel RTK pathways. Specifically, the directional effects of these pharmacogenetic factors are discussed with a focus on two commonly prescribed EGFR inhibitors: cetuximab and erlotinib. The results of this comprehensive review can be used to optimize the treatment of NSCLC with EGFR inhibitors. Furthermore, they may provide the rationale for the design of subsequent combination therapies that involve the inhibition of EGFR.
authors.affiliation: Biological Sciences Division, University of Chicago, Chicago, IL, 60637, USA. delaneyc@uchicago.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Delaney
authors.affiliation: Biological Sciences Division, University of Chicago, Chicago, IL, 60637, USA. samuelfrank@uchicago.edu.
authors.forename: Samuel
authors.initials: S
authors.lastname: Frank
authors.affiliation: Department of Medicine, University of Chicago, 900 E 57th street, KCBD room 7148, Chicago, IL, 60637, USA. rhuang@medicine.bsd.uchicago.edu.|The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, 315211, P. R. China. rhuang@medicine.bsd.uchicago.edu.
authors.forename: R Stephanie
authors.initials: RS
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents; D002289:Carcinoma, Non-Small-Cell Lung; D000068818:Cetuximab; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms; D009154:Mutation; D010597:Pharmacogenetics; D011799:Quinazolines
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab