Colorectal cancer carcinogenesis: From bench to bedside

Abstract

Colorectal cancer (CRC) remains one of the main causes of cancer death in developed countries. Yet, it is potentially preventable, by removing the precursor lesions - adenomas or serrated lesions. Several studies proved that this intervention reduces CRC mortality and that the first colonoscopy’s results can guide surveillance strategies. More recently, it became clear that several carcinogenesis pathways may lead to sporadic CRC. CRC is a heterogeneous disease, characterized by multiple molecular subtypes. Three main pathways have been implicated in the development of CRC: Chromosomal instability, microsatellite instability, and the “serrated” pathways, with overlapping features between them. This and other molecular and genetic based CRC classifications are known to have clinical implications, spanning from familial risk assessment to therapy choices. The authors review basic science data and provide insight on current implications for the management of patients with CRC.

Keywords: Colorectal cancer; Carcinogenesis pathways; Microsatellite instability; APC; KRAS; BRAF

Core Tip: Colorectal cancer (CRC) is a major cause of cancer death worldwide. It is a heterogeneous entity and its molecular and genetic features have clinical implications. Three main carcinogenesis pathways, with some overlapping features, are now known to lead to CRC: Chromosomal instability, microsatellite instability, and the “serrated” pathways. Their features, namely, microsatellite instability status and BRAF or KRAS mutation status, among others, have to be studied to assess familial cancer risk and to make adequate therapy choices. Ongoing research will potentially even enlarge basic science’s importance for clinical practice.