Medical Journal of The Islamic Republic of Iran (MJIRI)

Background: The narrative review aims to explore CRC pathogenesis by deciphering genetic-environmental interactions, analyzing the tumor microenvironment's role, and assessing treatment responses. These objectives seek to enhance clinical decision-making and improve CRC patient care through a comprehensive understanding of the disease.
   Methods: A narrative review from 2019 to 2024 on colorectal cancer (CRC) pathogenesis and treatment strategies was conducted. Systematic literature searches were performed on PubMed, using CRC-related keywords ("Colorectal Neoplasms"[Mesh]) AND "Tumor Microenvironment"[Mesh]. Screening yielded 233 eligible studies, with 14 highly relevant ones included. PRISMA guidelines were followed for transparency and reproducibility.
   Results: This narrative review spanning 2019-2024 shows diverse study designs (5 clinical studies, 4 randomized controlled trials, 2 cohort studies, and 3 systematic literature reviews) with varied sample sizes (from 14 to 4000 participants). Genetic mutations like KRAS and BRAF are significant in colorectal cancer pathogenesis, with 8% exhibiting MMR proficiency. Immune cells and paracrine signaling are influential, and therapeutic responses vary, with limited efficacy reported in certain combinations.
   Conclusion: This narrative review highlights CRC's multifactorial nature and complex tumor dynamics. Integrating genetic, environmental, and immune factors, personalized therapies are pivotal for efficacy. Continued research is crucial for optimizing treatments and improving patient outcomes, emphasizing the need for multifaceted, patient-tailored approaches in CRC management.