title: KRAS mutations as prognostic and predictive markers in non-small cell lung cancer.
abstract: A greater understanding of non-small-cell lung cancer at a molecular level has led to the identification of an increasing number of driver mutations. Extensive research of the KRAS gene as well as specific mutations has established its role in tumorigenesis. Nevertheless, the role of KRAS oncogene in non-small-cell lung cancer remains unclear. Recent studies indicated that mutant KRAS could be predictive of lack of response to chemotherapy, but large pooled analysis failed to confirm this result. The predictive value of KRAS mutation and EGFR-TKI treatment is more ambiguous with some recent evidence suggesting that it may be a negative predictive biomarker. This review provides an overview of RAS biology, assesses the utility of KRAS as a prognostic marker, and evaluates its role as a predictive marker for response to chemotherapy and EGFR-TKIs. In addition, we review some current studies that are targeting the KRAS pathway.
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Ontario, Canada. petra.martin@uhn.ca
authors.forename: Petra
authors.initials: P
authors.lastname: Martin
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D051231:Farnesyltranstransferase; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins