Molecular stratification of colorectal cancer populations and its use in directing precision medicine

Introduction: The intrinsic heterogeneity of colorectal cancer (CRC) makes it difficult to determine which patients will benefit from adjuvant or systemic therapy and which patients will not require further treatment beyond surgical resection. This had led to a generalized ‘one size fits all’ approach to therapy. Such heterogeneity also makes it a great challenge to predict which patients might respond to targeted therapies. Precision medical diagnostics now hold promise to address these new challenges.Areas covered: The authors first review various molecular/genomic classification studies of colorectal cancer, including the prognostic role of MSI (microsatellite instability), CIN (chromosomal instability), and driver genes such as KRAS, NRAS, BRAF, PIK3CA and TP53, as well as our recent finding revealing a new prognostic role of APC and partnering mutations with KRAS and TP53. The authors then discuss prediction of treatment response for either adjuvant therapy or systemic targeted therapy (e.g. anti-EGFR therapy) as well as the effect of tumor sidedness.Expert commentary: There is an urgent need for more precise molecular classification to stratify adjuvant therapy and systemic targeted therapy to ultimately facilitate individualized treatments. Sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC patients.