Recent progress in clinical and molecular biological research in rectal serrated lesions

Colorectal cancer ranks among the most common malignancies worldwide. Rectal serrated lesions represent a significant precancerous condition, accounting for approximately 30% of sporadic colorectal carcinomas. Their flat morphology and indistinct borders often lead to missed detection during routine colonoscopy. In addition, the complex classification system and considerable molecular heterogeneity of these lesions create challenges for clinical management, including diagnostic accuracy, risk stratification, and treatment decisions. Research in recent years has progressively clarified the unique oncogenic pathway associated with serrated lesions-referred to as the serrated pathway. Characteristic molecular events include mutations in b-raf murine sarcoma viral oncogene homolog B (BRAF) or kirsten rat sarcoma viral proto-oncogene (KRAS) mutations, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI). Among these, the BRAF V600E mutation serves as the core driver event. Combination therapy with encorafenib and cetuximab, which targets this mutation, has been shown to improve outcomes in patients with BRAF-mutated metastatic colorectal cancer. Furthermore, Microsatellite Instability-High (MSI-H) lesions exhibit sensitivity to immune checkpoint inhibitors, offering novel options for personalized treatment. Concurrently, the application of technologies such as artificial intelligence (AI)-assisted endoscopy, molecular imaging, and liquid biopsy holds promise for improving the detection of early-stage lesions. This systematic review examines the current research landscape regarding rectal serrated lesions, covering an evolution of classification systems, elucidation of molecular and cellular mechanism, advances in diagnostic technology, and optimized treatment strategies. We further discussed molecular differences between the serrated pathway and the classical adenoma-carcinoma sequence, epigenetic regulatory mechanisms, tumour microenvironment characteristics, and personalized management strategies based on molecular subtyping. By synthesizing existing evidence, this review aims to provide theoretical guidance for the clinical management of rectal serrated lesions and lay the groundwork for future research.