Recent Advances in Our Knowledge of mCRC Tumor Biology and Genetics: A Focus on Targeted Therapy Development

Metastatic colorectal cancer (mCRC) remains a highly lethal malignancy although considerable progress has resulted from characterizing molecular alterations such as RAS mutation status and extent of microsatellite instability (MSI) to guide optimal use of available therapies. The availability of gene expression profiling, next generation sequencing technologies, proteomics analysis and other technologies provides high resolution information on individual tumors, including metastatic lesions to better define intra-tumor and inter-tumor heterogeneity. Recent literature applying this information to further customize personalized therapies is reviewed. Current biomarker-based stratification used to select optimal therapy that is personalized to the mutation profile of individual tumors is described. Recent literature using whole exome sequencing of metastatic lesions and primary CRC tumors and other advanced technologies to more fully elucidate the tumor biology specific to mCRC sub-types and to develop more precise therapies that improve outcomes is also reviewed.