Colorectal Cancer: Basic and Translational Research

Abstract

Background: Colorectal cancer (CRC) still accounts for high mortality and morbidity of cancer patients worldwide. Early detection screening and therapeutic management of CRC are still traditional, with some important progress including cetuximab, microsatellite instability and the concept of CRC intrinsic subtypes. Summary: Most achievements are derived from translational cancer research. Translational cancer research attempts to better understand the heterogeneity of human cancer and further turn discoveries into benefits for cancer patients. The four basic strategies of translational research can be depicted as (a) biomarker discovery, (b) identification in xenografts, (c) population-based verification and (d) clinical validation. Key Message Translational research has led to significant benefits in the screening and management of patients with colorectal cancer, such as the identification of responders to cetuximab therapy, and the application of microsatellite instability and intrinsic subtyping of colorectal cancers towards personalized therapy. Practical Implications The process of translational research involves four basic strategies: (a) biomarker discovery, (b) identification of the biomarkers in xenografts, (c) population-based verification and (d) clinical validation. Several prognostic biomarkers, namely SPARCL1, HMGA2, RRM2 and SOX2, have been successfully identified following these strategies. To address the problem of treatment failure, therapy should be adapted to the molecular phenotype and colorectal cancer intrinsic subtype of the tumor. A case in point is the presence of mutated KRAS, which can be used to identify non-responders to cetuximab therapy. Likewise, microsatellite instability is a strong predictor of response to fluorouracil-based adjuvant chemotherapy in stage II and III colon cancer. A comprehensive classification of the intrinsic subtypes of colorectal cancer not only enhances our understanding of response to therapy and prognosis, but also enables treatment to be tailored to the individual patient.