Epidermal Growth Factor Inhibitors
The EGFR receptor (EGFR) is a member of the HER family of receptor tyrosine kinases that includes EGFR itself (ErbB1/HER1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4). These proteins are classic membrane-bound tyrosine kinase receptors whose activation is typically ligand dependent. The principal ligands for EGFR are EGF and TGF-α. Other ligands include amphiregulin, heparin-binding EGF, the poxvirus mitogens, epiregulin, and β-cellulin.
EGFR Activation and Downstream Signaling
Receptor activation results in homo- or heterodimerization and autophosphorylation of c-terminal tyrosine residues. Receptor activation enables the docking of cytoplasmic proteins that bind to specific phosphotyrosine residues and initiate several cell signaling pathways. These pathways include the Ras-Raf-MAPK pathway, the PI3K-AKT pathway, the protein kinase C pathway, the STAT pathway, and the src kinase pathway, all of which play important roles in tumor cell proliferation,...
KeywordsRectal Cancer National Comprehensive Cancer Network Keyhole Limpet Hemocyanin EGFR Mutation EGFR Activation
- Dewdney A, Cunningham D, Tabernero J, Capdevila J, Glimelius B, Cervantes A, Tait D, Brown G, Wotherspoon A, Gonzalez de Castro D, Chua YJ, Wong R, Barbachano Y, Oates J, Chau I (2012) Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol 30(14):1620–1627. doi:10.1200/JCO.2011.39.6036. Epub 2 Apr 2012CrossRefPubMedGoogle Scholar
- Eberhard DA, Johnson BE, Amler LC et al (2005) Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23:5900CrossRefPubMedGoogle Scholar
- Ramalingam SS et al (2015) AZD9291, a mutant-selective EGFR inhibitor, as first-line treatment for EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): results from a phase 1 expansion cohort. J Clin Oncol 33 (suppl): abstr 8000Google Scholar
- Reardon DA, Schuster J, Tran DD, Fink KL, Nabors LB, Li G, Bota DA, Lukas RV, Desjardins A, Ashby LS, Duic JP, Mrugala MM, Werner A, Hawthorne T, He Y, Green JA, Yellin MJ, Turner CD, Davis TA, Sampson JH, The ReACT Study Group (2015) ReACT: Overall survival from a randomized phase II study of rindopepimut (CDX-110) plus bevacizumab in relapsed glioblastoma. J Clin Oncol 33(15):2009Google Scholar
- Schuster J, Lai RK, Recht LD, Reardon DA, Paleologos NA, Groves MD, Mrugala MM, Jensen R, Baehring JM, Sloan A, Archer GE, Bigner DD, Cruickshank S, Green JA, Keler T, Davis TA, Heimberger AB, Sampson JH (2015) A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study. Neuro Oncol 17(6):854–861CrossRefPubMedPubMedCentralGoogle Scholar
- Tournigand C et al (2015) Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol. doi: 10.1016/S1470-2045(15)00216-8. Published online 13 Oct 2015Google Scholar