Colorectal Cancer Pathogenesis and Treatment Strategies: Insights into the Role of p53

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide.Its development results from cumulative somatic and genetic alterations that disrupt normal cell division and promote uncontrolled proliferation.Genetic and epigenetic modifications, particularly mutations in tumor suppressor genes such as TP53, are key drivers of CRC.Most CRCs are adenocarcinomas, and the CMS4 molecular subtype is characterized by enhanced stromal invasion and epithelialmesenchymal transition (EMT), mainly regulated through the TGF- signaling pathway.This narrative review aims to highlight the molecular mechanisms underlying CRC pathogenesis, with a specific focus on the Role of p53, and to explore emerging gene therapy strategies targeting these pathways.This study is a narrative review based on a comprehensive search of articles published from 2000 to 2024 in PubMed, Scopus, and Web of Science.Keywords included "colorectal cancer," "p53," "gene therapy," "CMS4," "WNT/-catenin," and "angiogenesis."Selected articles were reviewed for relevance to the pathogenesis and targeted treatment approaches in CRC.Alterations in WNT/-catenin signaling, cell cycle regulators, and apoptotic pathways are commonly observed in CRC.p53 mutations significantly affect tumor progression and response to therapy.Gene therapy approaches using adenoassociated virus (AAV) vectors to deliver anti-angiogenic genes such as angiostatin and endostatin offer novel therapeutic potential, with reduced side effects and improved targeting of tumor pathways.Targeting molecular abnormalities, especially those involving p53, may enhance CRC treatment efficacy.Gene-based strategies represent a promising direction in personalized CRC therapy.