The Molecular Basis of Metastatic Colorectal Cancer

Purpose of Review: Metastatic colorectal cancer (CRC) is a vexing clinical problem. In contrast to early-stage disease, once CRC metastasizes to other organs, long-term survival is compromised. We seek to review the molecular pathogenesis, animal models, and functional genomics for an enhanced understanding of how CRC metastasizes and how this can be exploited therapeutically. Recent Findings: Mouse models may recapitulate certain aspects of metastatic human CRC and allow for studies to identify regulators of metastasis. Modulation of transcription factors, onco-proteins, or tumor suppressors has been identified to activate known metastatic pathways. CD44 variants, microRNAs, and RNA binding proteins are emerging as metastatic modulators. Summary: CRC metastasis is a multi-faceted and heterogeneous disease. Despite common pathways contributing to metastatic development, there are numerous variables that modulate metastatic signals in subsets of patients. It is paramount that studies continue to investigate metastatic drivers, enhancers, and inhibitors in CRC to develop therapeutic targets and improve disease outcomes.