Implications of KRAS mutation status for the treatment of metastatic colorectal cancer.
Targeted agents have become an integral part of the treatment of a number of malignant diseases and regimens containing agents that disrupt the epidermal growth factor receptor (EGFR) signaling pathway are now considered a standard therapeutic approach for a range of tumor types. Recently, the mutational status of the KRAS gene in tumors was shown to be predictive of outcome to treatment with EGFR-targeted therapies in metastatic colorectal cancer (mCRC). The immoglobulin (Ig) G1 EGFR-targeting monoclonal antibody (mAb), cetuximab, has been shown to provide significant clinical benefits when added to standard irinotecan- and oxaliplatin-containing chemotherapy regimens, first-line, in patients with KRAS wild-type mCRC. Its effects on tumor response and resectability of metastases make cetuximab a particularly useful treatment option for patients with bulky or initially unresectable disease. With an ever-increasing array of management options available, it is important that patients with mCRC receive the treatment that offers them the best chance of prolonged survival. In view of this, testing for tumor KRAS mutation status should be mandatory at diagnosis of mCRC, prior to treatment decision-making.
Ciardiello
Fortunato
F
Division of Medical Oncology, Department of Experimental and Clinical Medicine and Surgery F. Magrassi and A. Lanzara, Second University of Naples, Naples, Italy. fortunato.ciardiello@unina2.it
Tejpar
Sabine
S
Papamichael
Demetris
D
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D002166:Camptothecin / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000503:physiopathology; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011905:Genes, ras / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D000077146:Irinotecan; D009154:Mutation; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077150:Oxaliplatin; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome; D018631:ras Proteins / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D047428:Protein Kinase Inhibitors; D000077150:Oxaliplatin; D000077146:Irinotecan; D066246:ErbB Receptors; D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin