Use of K-Ras as a predictive biomarker for selecting anti-EGF receptor/pathway treatment.
Ras protein is a downstream regulator of multiple cellular receptor tyrosine kinases, mediating cell growth, transformation and maintenance of the malignant phenotype in several human cancers. Oncogenic gain-of-function mutations in ras frequently occur in colorectal cancer, non-small-cell lung cancer and pancreatic cancers. Recent clinical studies of colorectal cancer have revealed that the therapeutic efficacy of cetuximab, a chimeric monoclonal antibody against EGF receptor, depends on the presence of wild-type k-ras. Additional studies in non-small-cell lung cancer have suggested that the k-ras mutation may be a negative predictor of response to the EGF receptor tyrosine kinase inhibitors erlotinib and gefitinib. These observations have provoked an interest in utilizing K-Ras as a predictive biomarker, allowing clinicians to direct the therapy of cancer patients based on their mutational status of the k-ras gene.
Jiang
Yixing
Y
Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA 17033, USA.
Mackley
Heath
H
Cheng
Hua
H
Ajani
Jaffer A
JA
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011905:Genes, ras; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins