Selection criteria for c-Met-targeted therapies: emerging evidence for biomarkers

Extensive development of targeted therapies emphasize the critical need for biomarkers and major efforts have been engaged to identify screening, prognostic, stratification and therapy-monitoring markers. One of the challenges in translating preclinical studies into effective clinical therapies remains the accurate identification of a responsive subsets of patients. Studies on trastuzumab demonstrated that patient response could be specifically correlated with the amplification of the Her2 gene. However, for the EGF receptor, it has been more difficult to find the right stratification biomarker and recent data demonstrate that genetic alterations for the EGF receptor have to be considered. Taken together, these data underline the need for a deeper understanding of both targeted receptor and human disease to determine pathways that might be investigated during early clinical trials in order to define relevant biomarkers for patient selection. This article, dealing with the c-Met tyrosine kinase receptor, provides an overview of c-Met alterations observed in cancer and proposes approaches for stratification biomarker selection.