title: Influence of polymorphisms on EGFR targeted therapy in non-small-cell lung cancer.
abstract: Non-small-cell-lung cancer (NSCLC) is the leading cause of cancer-related deaths. However, chemotherapy has reached a therapeutic plateau and deals with significant toxicity. Novel anticancer treatments to neutralize specific molecules or genes involved in cancer development ("targeted-therapy") are being developed to reduce side-effects and improve outcome. The epidermal-growth-factor receptor (EGFR) is over-expressed in NSCLC and emerged as an attractive target. Two classes of anti-EGFR agents (tyrosine-kinase-inhibitors and monoclonal antibodies) have shown clinical activity, depending on EGFR mutations and expression. However, clinical outcome, including tolerability, can not always be explained by these biomarkers. Thus, the identification of novel biomarkers is a viable area of research. Germline polymorphisms can be easily assessed, and polymorphisms in EGFR, AKT1 and ABCG2 have been correlated with outcome and toxicity in NSCLC patients given anti-EGFR therapies. However, there is lack of unanimity in findings, influenced by differences in study design/analysis, and the prognostic/predictive role of these polymorphisms needs to be evaluated within prospective studies. Finally, there is a critical need to conduct more studies on the relation of genotype with drug concentration/activity.
authors.affiliation: Department Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.forename: Lale
authors.initials: L
authors.lastname: Erdem
authors.forename: Efnan
authors.initials: E
authors.lastname: Olcay
authors.forename: Leticia G
authors.initials: LG
authors.lastname: Leon
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
mesh_terms: D000911:Antibodies, Monoclonal / Q000235:genetics; D061067:Antibodies, Monoclonal, Humanized; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005076:Exanthema / Q000139:chemically induced; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011110:Polymorphism, Genetic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D000068818:Cetuximab; D000077156:Gefitinib