Elucidating the molecular aspects of colorectal cancer and their clinical importance

Over the last 10 years, crucial improvements have been made in the pursuit of more effective therapies for colorectal cancer (CRC). In understanding the basis of CRC biology we have evolved from the classical ‘adenoma to carcinoma transition’ hypothesis, to the identification of two CRC clusters (microsatellite instability and chromosomal instability) and further classifications based on epigenetic events. Thanks to these advances in molecular analyses, key pathways, notably that of the EGFR, are now integrated into standard practice for therapeutic management and other pathways are being explored for blocking driving mutations and overcoming drug resistance. Genetic profiling is being developed to better predict prognosis and treatment response. The CRC subtyping consortium has combined and reanalyzed genetic signature data sets from several international groups. A definitive genetic CRC classification is currently being established and will be critical for clinical development of therapeutic strategies.