KRAS mutational testing in the selection of patients for EGFR-targeted therapies.
The small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the anti-EGFR monoclonal antibodies have proven activity in lung and colorectal adenocarcinomas, respectively, but only a small fraction of patients exhibit significant responses. The observation that only a minority of patients respond to EGFR-targeted therapies, in combination with their toxicity and high costs, has driven the search for molecular markers predictive of response. The main focus of the present review is the recent discovery that mutations in the KRAS oncogene constitute a negative predictive marker in this clinical setting, namely that their presence can be used to predict which patients are unlikely to benefit from treatment with EGFR-directed therapy.
Garcia
Joaquin
J
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Riely
Gregory J
GJ
Nafa
Khedoudja
K
Ladanyi
Marc
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins