Preclinical Models of Colorectal Cancer Liver Metastasis: Therapeutic Evaluation and Translational Implications

Ye Ri Han1, Sang Bong Lee2,3,4

  • 1Department of Chemistry, Duksung Women's University, Seoul, Republic of Korea.

Oncology Research
|June 26, 2026
PubMed

Insights

Developing better preclinical models is crucial for improving colorectal cancer liver metastasis (CRLM) treatments. This review evaluates current models and suggests principles for selecting the best ones to enhance clinical success.

Area of Science:

  • Oncology
  • Translational Research
  • Preclinical Modeling

Background:

  • Colorectal cancer liver metastasis (CRLM) is a major cause of cancer mortality, with limited treatment efficacy due to biological heterogeneity.
  • Current preclinical models often lack biological fidelity, leading to discrepancies between experimental findings and clinical outcomes.
  • Advances in systemic therapy, immunotherapy, and liver-directed interventions have not fully translated to improved patient benefit.

Purpose of the Study:

  • To critically review existing preclinical platforms for studying CRLM.
  • To evaluate how different models influence therapeutic assessment and predict clinical responses.
  • To propose principles for rational model selection to enhance translational success in CRLM research.

Main Methods:

  • Examination of orthotopic and metastatic models that mimic hepatic colonization and tumor microenvironment.
  • Evaluation of methodological innovations like tissue adhesive-based implantation and biomaterial-assisted strategies.
  • Analysis of how various models impact the assessment of systemic, immune-based, metabolic, and liver-directed treatments.

Main Results:

  • Therapeutic efficacy in CRLM is highly model-dependent, with significant discrepancies between preclinical data and clinical outcomes.
  • Orthotopic and metastatic models show promise in recapitulating key aspects of CRLM, including tumor-microenvironment interactions and immune regulation.
  • Methodological innovations can enhance the anatomical fidelity and reproducibility of preclinical models.

Conclusions:

  • Current preclinical platforms for CRLM have distinct strengths and limitations that affect their ability to predict clinical responses.
  • Rational selection of appropriate models is essential for improving the translation of preclinical findings to clinical benefit.
  • Further development and validation of high-fidelity models are needed to accelerate progress in CRLM therapeutics.