Transplantable Orthotopic Mouse Models for Colorectal Cancer Research: Current Strategies and Future Directions

Background: Colorectal cancer (CRC) remains a leading cause of cancer mortality, and metastatic disease still carries a poor prognosis, highlighting the need for preclinical models that better reflect human tumor biology. Orthotopic murine CRC models more closely recapitulate the native tumor microenvironment and metastatic routes than subcutaneous or in vitro systems. Summary: In this review, we summarize transplantable orthotopic CRC mouse models and discuss their establishment techniques, applications, and limitations. A systematic literature search was performed in PubMed using the terms “murine colorectal cancer model”, “orthotopic colorectal cancer”, “cecal implantation”, “rectal cancer mouse model”, and “tumor organoid transplantation”. We describe commonly used approaches, including open surgical implantation and minimally invasive transanal methods, and compare key design choices such as tumor source (syngeneic vs. xenograft), implantation site, and readouts for local growth and metastasis. We also highlight practical considerations, including immune competence and technical complexity that influence reproducibility and model selection for specific research questions. Key messages: Transplantable orthotopic models are indispensable for studying site specific tumor-host interactions and metastasis in CRC. Model choice should be guided by the intended biological question, immune context, and procedural feasibility. Continued refinement and standardization, including integration of immune and microenvironmental components, will further improve translational relevance.