Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy.
Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS) status has emerged as a predictor of response to epidermal growth factor receptor (EGFR) targeted therapies. In this article, we will discuss targeted therapies for colorectal cancers (CRC) based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response) to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients with colorectal cancer whose tumor has an activating mutation in KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should now become a standard practice that any patients being considered for EGFR targeted therapies have their tumors tested for KRAS status and only those with wild-type KRAS being offered such therapies.
Chang
David Z
DZ
Departments of Gastrointestinal Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. David.Chang@USOncology.com
Kumar
Vikas
V
Ma
Ying
Y
Li
Kuiyuan
K
Kopetz
Scott
S
D000970:Antineoplastic Agents / Q000008:administration & dosage; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D057285:Precision Medicine / Q000379:methods* / Q000639:trends; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins