Biology and preclinical models of colorectal cancer metastasis

Yoojeong Seo1, Jinho Jang1, Jae-Il Park1,2,3

  • 1Division of Radiation Oncology, Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Intestinal Research
|March 26, 2026
PubMed

Insights

Investigating metastatic colorectal cancer (mCRC) requires better experimental models. Current systems have limitations in capturing the full metastatic cascade and tumor microenvironment for developing effective therapies.

Area of Science:

  • Oncology
  • Cancer Metastasis Research

Background:

  • Metastatic colorectal cancer (mCRC) is a leading cause of cancer mortality.
  • The complex biology of mCRC, including metastasis, remains poorly understood.
  • Existing research provides limited insight into how primary tumors metastasize.

Purpose of the Study:

  • To review current experimental systems for studying mCRC.
  • To discuss the strengths and limitations of various models in capturing metastatic processes.
  • To identify gaps in modeling and propose integrated approaches for future research.

Main Methods:

  • Review of existing literature on experimental models for mCRC.
  • Analysis of genetically engineered mouse models, carcinogen-induced models, transplant models, patient-derived organoids, and xenografts.
  • Discussion of challenges in longitudinal sampling and modeling of tumor microenvironment.

Main Results:

  • Current experimental systems partially capture key steps of the metastatic cascade.
  • Significant limitations exist in modeling immune and stromal influences.
  • Obstacles hinder longitudinal sampling and quantitative assessment of metastatic burden.

Conclusions:

  • Improved experimental systems are crucial for understanding mCRC metastasis.
  • Integrating emerging approaches like single-cell transcriptomics and advanced tracking methods is needed.
  • A comprehensive framework is required to link mechanistic insights to clinical behavior and develop metastasis-specific therapies.