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Updated: Jun 5, 2025

Assessing Cell Viability and Death in 3D Spheroid Cultures of Cancer Cells
Published on: June 16, 2019
Breaking the mold: 3D cell cultures reshaping the future of cancer research
Sandra Cordeiro1,2, Beatriz B Oliveira1,2, Ruben Valente1,2
1UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Caparica, Portugal.
Abstract:
Despite extensive efforts to unravel tumor behavior and develop anticancer therapies, most treatments fail when advanced to clinical trials. The main challenge in cancer research has been the absence of predictive cancer models, accurately mimicking the tumoral processes and response to treatments. The tumor microenvironment (TME) shows several human-specific physical and chemical properties, which cannot be fully recapitulated by the conventional 2D cell cultures or the in vivo animal models. These limitations have driven the development of novel in vitro cancer models, that get one step closer to the typical features of in vivo systems while showing better species relevance. This review introduces the main considerations required for developing and exploiting tumor spheroids and organoids as cancer models. We also detailed their applications in drug screening and personalized medicine. Further, we show the transition of these models into novel microfluidic platforms, for improved control over physiological parameters and high-throughput screening. 3D culture models have provided key insights into tumor biology, more closely resembling the in vivo TME and tumor characteristics, while enabling the development of more reliable and precise anticancer therapies.
Insights
Advanced cancer models like tumor spheroids and organoids better mimic the human tumor microenvironment (TME). These 3D models improve drug screening and personalized medicine, leading to more effective anticancer therapies.
Area of Science:
- Oncology
- Biotechnology
- Biomedical Engineering
Background:
- Conventional 2D cell cultures and animal models fail to accurately replicate the human tumor microenvironment (TME).
- This limitation hinders the development of effective anticancer therapies, as most treatments fail in clinical trials.
- There is a critical need for predictive cancer models that mimic in vivo conditions more closely.
Purpose of the Study:
- To review the development and application of tumor spheroids and organoids as advanced in vitro cancer models.
- To explore their utility in drug screening and personalized medicine.
- To discuss the integration of these 3D models into microfluidic platforms.
Main Methods:
- Review of current literature on 3D cell culture techniques, specifically tumor spheroids and organoids.
- Analysis of the advantages of these models over traditional methods for studying tumor biology.
- Examination of the incorporation of 3D models into microfluidic systems for enhanced control and throughput.
Main Results:
- 3D culture models, including spheroids and organoids, offer improved recapitulation of in vivo tumor characteristics and the TME.
- These models demonstrate significant potential for more accurate drug screening and the advancement of personalized medicine.
- Integration with microfluidic platforms enhances experimental control and enables high-throughput screening capabilities.
Conclusions:
- Tumor spheroids and organoids represent a significant advancement in in vitro cancer modeling.
- These 3D models are crucial for gaining deeper insights into tumor biology and developing more reliable anticancer therapies.
- The transition to microfluidic-integrated 3D models promises more precise and efficient preclinical drug development.

