Multidisciplinary Cancer Investigation

en Colorectal Cancer Pathogenesis and Treatment Strategies: Insights into the Role of p53 Molecular Mechanisms Review Article <div style="text-align: justify;">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 epithelial-mesenchymal transition (EMT), mainly regulated through the TGF-β 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/β-catenin," and "angiogenesis." Selected articles were reviewed for relevance to the pathogenesis and targeted treatment approaches in CRC. Alterations in WNT/β-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 adeno-associated 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.</div> Colorectal cancer, p53, Gene therapy, EMT, CMS4 1 19 http://mcijournal.com/browse.php?a_code=A-10-691-4&slc_lang=en&sid=1 Mohammad Kordkatouli mohammad.kordkatouli@outlook.com 10031947532846004171 0009000630086820 No Department of Cell and Molecular Biology , GO.C, Islamic Azad University, Gorgan, Iran Mahmoud Heidari Mahmoud.heidari@iau.ac.ir 10031947532846004172 0000000291032491 Yes Department of Biology, GO.C, Islamic Azad University, Gorgan, IranMedicinal plants research center, GO.C, Islamic Azad University, Gorgan, Iran Nasrinsadat Azami Na.azami@iau.ac.ir 10031947532846004173 0000000245497220 No Department of Biology, Faculty of Science, GO.C, Islamic Azad University, Gorgan, IranMedicinal Plants Research Center, GO.C, Islamic Azad University, Gorgan, Iran Javad Poursamimi javadpoursamimi@gmail.com 10031947532846004174 0000000287264425 No Department of Immunology, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran