REVIEW article

Front. Genet.

Sec. Cancer Genetics and Oncogenomics

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1545017

This article is part of the Research Topic3D in Vitro Models - A New Era in Cancer ResearchView all articles

In vitro 3D modeling of colorectal cancer: the pivotal role of the extracellular matrix, stroma and immune modulation

Provisionally accepted
  • 1Malmö University, Malmö, Sweden
  • 2KTH Royal Institute of Technology, Division of Protein Technology, Stockholm, Sweden, Stockholm, Sweden
  • 3Kristianstad University, Kristianstad, Skane County, Sweden

The final, formatted version of the article will be published soon.

Colorectal cancer (CRC) is a leading global cancer with high mortality, especially in metastatic cases, with limited therapeutic options. The tumor microenvironment (TME), a network comprising various immune cells, stromal cells and extracellular (ECM) components plays a crucial role in influencing tumor progression and therapy outcome. The genetic heterogeneity of CRC and the complex TME complicates the development of effective, personalized treatment strategies. The prognosis has slowly improved during the past decades, but metastatic CRC (mCRC) is common among patients and is still associated with low survival. The therapeutic options for CRC differ from those for mCRC and include surgery (mostly for CRC), chemotherapy, growth factor receptor signaling pathway targeting, as well as immunotherapy. Malignant CRC cells are established in the TME, which varies depending on the primary or metastatic site. Herein, we review the role and interactions of several ECM components in 3D models of CRC and mCRC tumor cells, with an emphasis on how the TME affects tumor growth and treatment. This comprehensive summary provides support for the development of 3D models that mimic the interactions within the TME, which will be essential for the development of novel anticancer therapies.

Keywords: colorectal cancer, in vitro, 3D model, Tumor Microenvironment, Extracellular Matrix, immune cells, therapy Font: Italic Formatted: Font: Italic Formatted: Font: Italic Formatted: Normal, Space After: 8 pt

Received: 13 Dec 2024; Accepted: 23 Apr 2025.

Copyright: © 2025 Hanitrarimalala, Prgomet, Hedhammar, Tassidis and Gjörloff Wingren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Anette Gjörloff Wingren, Malmö University, Malmö, Sweden

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