title: Targeting mechanisms of resistance to anti-EGF receptor therapy in KRAS wild-type colorectal cancer: the path to more personalized medicine.
abstract: The targeting of EGF receptors (EGFRs) in metastatic colorectal cancer has improved the outcome of patients with KRAS wild-type tumors. However, these improvements have been modest and do not translate across all patients with KRAS wild-type tumors. Better understanding of the EGFR pathway has led to the exploration of variable novel potential biomarkers of resistance and response to anti-EGFR therapy. This manuscript will focus on recently identified mechanisms of resistance to anti-EGFR therapy in KRAS wild-type colorectal cancer. Subsequently, an assessment will be presented on how the current understanding of some of these mechanisms of resistance has led, and will lead, to novel therapeutic opportunities in the management of colorectal cancer.
authors.affiliation: City of Hope, 1500 E Duarte Road, Building 51, Room 127, Duarte, CA 91010, USA. mfakih@coh.org
authors.forename: Marwan
authors.initials: M
authors.lastname: Fakih
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000276:immunology; D020558:GTP Phosphohydrolases / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D057285:Precision Medicine / Q000379:methods; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D020558:GTP Phosphohydrolases; D008565:Membrane Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D048493:Proto-Oncogene Proteins B-raf; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C491743:MET protein, human; C482119:BRAF protein, human; C494929:PTEN protein, human; C579846:NRAS protein, human