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A 3D View of Colorectal Cancer Models in Predicting Therapeutic Responses and Resistance
Eileen Reidy1,2,3,4, Niamh A Leonard1,2,3, Oliver Treacy1,2,3
1Lambe Institute for Translational research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 V4AY Galway, Ireland.
Abstract:
Although there have been many advances in recent years for the treatment of colorectal cancer (CRC), it still remains the third most common cause of cancer-related deaths worldwide. Many patients with late stage CRC display resistance to multiple different therapeutics. An important aspect in developing effective therapeutics for CRC patients is understanding the interactions that take place in the tumor microenvironment (TME), as it has been shown to contribute to drug resistance in vivo. Much research over the past 100 years has focused on 2D monolayer cultures or in vivo studies, however, the efficacy in translating these to the clinic is very low. More recent studies are turning towards developing an effective 3D model of CRC that is clinically relevant, that can recapitulate the TME in vitro and bridge the gap between 2D cultures and in vivo studies, with the aim of reducing the use of animal models in the future. This review summarises the advantages and limitations of different 3D CRC models. It emphasizes how different 3D models may be optimised to study cellular and extracellular interactions that take place in the TME of CRC in an effort to allow the development of more translatable effective treatment options for patients.
Insights
Three-dimensional (3D) colorectal cancer (CRC) models offer a promising in vitro approach to study the tumor microenvironment (TME) and overcome drug resistance, potentially reducing animal testing.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Research
Background:
- Colorectal cancer (CRC) remains a leading cause of cancer death globally, with significant challenges in treating late-stage disease due to therapeutic resistance.
- Tumor microenvironment (TME) interactions are critical in CRC progression and drug resistance, but traditional 2D cultures and in vivo models have limited clinical translatability.
- There is a need for advanced in vitro models that accurately recapitulate the TME for CRC drug development.
Purpose of the Study:
- To review the advantages and limitations of various 3D colorectal cancer (CRC) models.
- To highlight the potential of 3D models in studying tumor microenvironment (TME) interactions in CRC.
- To emphasize optimizing 3D models for developing more translatable and effective CRC therapeutics.
Main Methods:
- Review of existing literature on 3D colorectal cancer (CRC) models.
- Analysis of the ability of different 3D models to recapitulate the tumor microenvironment (TME) in vitro.
- Evaluation of the translatability of 3D CRC models compared to 2D cultures and in vivo studies.
Main Results:
- 3D colorectal cancer (CRC) models show greater potential than 2D cultures for mimicking the tumor microenvironment (TME) and predicting therapeutic responses.
- Different 3D models possess unique advantages and limitations in recapitulating complex cellular and extracellular interactions within the TME.
- Optimizing 3D CRC models can bridge the gap between preclinical research and clinical application, potentially reducing reliance on animal models.
Conclusions:
- Advanced 3D colorectal cancer (CRC) models are crucial for understanding tumor microenvironment (TME) dynamics and overcoming therapeutic resistance.
- Further optimization of 3D CRC models is needed to enhance their clinical relevance and facilitate the development of novel treatment strategies.
- These models hold promise for improving drug discovery and reducing the need for animal testing in CRC research.
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