Use of K-Ras as a predictive biomarker for selecting anti-EGF receptor/pathway treatment

Abstract

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.