Serrated colorectal cancer: preclinical models and molecular pathways

Serrated lesions are histologically heterogeneous, and detection can be challenging as these lesions have subtle features that may be missed by endoscopy. Furthermore, while approximately 30% of colorectal cancers (CRCs) arise from serrated lesions, only 8-10% of invasive serrated CRCs exhibit serrated morphology at presentation, suggesting potential loss of apparent characteristics with increased malignancy. Thus, understanding the genetic basis driving serrated CRC initiation and progression is critical to improve diagnosis and identify therapeutic biomarkers and targets to guide disease management. This review discusses the preclinical models of serrated CRCs reported to date and how these systems have been used to provide mechanistic insights into tumor initiation, progression, and novel treatment targets.