Organotropic metastasis in colorectal cancer: integrating molecular pathways with therapeutic opportunities

Colorectal cancer (CRC), characterized by high incidence and mortality rates, is an aggressive malignancy that significantly burdens public health. Metastasis represents the principal factor contributing to treatment failure in CRC patients, largely due to limited comprehension of the underlying mechanisms governing this phenomenon. CRC metastasis involves multiple factors, including dynamics within the tumor microenvironment (TME), epithelial-mesenchymal transition (EMT), and the dissemination of cancer cells through the circulatory and lymphatic systems. These mechanisms are regulated by complex molecular interactions. A deeper understanding of the metastatic processes and the identification of viable therapeutic targets could substantially advance innovative clinical interventions. This review highlights key contributors to CRC metastasis, integrates relevant molecular mechanisms with distinct patterns of organ-specific spread, and emphasizes the latest advancements in this field. Additionally, it explores experimental models of CRC and metastasis, provides mechanistic insights, and addresses challenges in the clinical management of metastatic CRC. This article aims to facilitate future research and highlight promising therapeutic opportunities for clinical translation.