MINI REVIEW article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicEditors’ Showcase 2024: Insights in Cancer Cell BiologyView all 7 articles
From Mono-to Multi-Cellular In Vitro Models: Reconstructing Colorectal Cancer Complexity for Translational and Personalized Applications
Provisionally accepted
Pier Giorgio Amendola1,2*
Gareth Owain Edwards2
Francesco Saverio Li Causi3Giorgio Castagnola3Shailendra Singh2- 1R&D Pharmacon, Sutri, Italy
- 2Cellomatics Biosciences Ltd, Nottingham, United Kingdom
- 3Azienda Ospedaliera Sant'Andrea, Rome, Italy
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Colorectal cancer (CRC) is a clinically and biologically heterogeneous disease shaped by diverse molecular subtypes, tumour microenvironmental contexts, and rapid adaptation under therapeutic pressure. Despite advances in screening, molecular profiling, and targeted and immune-based therapies, outcomes remain highly variable, particularly in microsatellite-stable disease, where immune exclusion and resistance mechanisms limit durable benefit. This complexity is only partially captured by current biomarkers and contributes to late-stage failure in drug development and suboptimal patient stratification in the clinic. This Mini Review discusses how advanced in vitro models can better recapitulate CRC pathophysiology and generate decision-relevant evidence for both translational research and precision oncology. We highlight the added value of three-dimensional patient-derived organoids, heterotypic co-cultures, organ-on-chip platforms, and ex vivo tissue models. These approaches preserve key features of CRC, including architecture, clonal diversity, stromal and immune crosstalk, diffusion barriers, and exposure dynamics, enabling mechanistic studies, rational combination testing, and functional drug-response profiling. Integrating fit-for-purpose in vitro systems into translational workflows can help de-risk therapeutic development and support more personalized, effective treatment strategies for CRC patients.
Keywords: Co-culture models, colorectal cancer, organ-on- a-chip, Patient derived organoids, precision oncology, tumor micreoenvironment (TME)
Received: 29 Dec 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Amendola, Edwards, Saverio Li Causi, Castagnola and Singh. 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: Pier Giorgio Amendola
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