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Updated: May 20, 2026
Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening
Published on: September 5, 2018
The multicellular tumor spheroid model for high-throughput cancer drug discovery
Daniel V LaBarbera1, Brian G Reid, Byong Hoon Yoo
1The University of Colorado Denver, The Skaggs School of Pharmacy and Pharmaceutical Sciences the University of Colorado AMC, The Department of Pharmaceutical Sciences, 12850 East Montview Blvd Aurora Colorado C238, USA. Daniel.LaBarbera@ucdenver.edu
Introduction:
For the past 30 years 2D-cell-based assay models have dominated preclinical cancer drug discovery efforts. 2D-cell-based models fail to predict in vivo efficacy, contributing to a lower success rate and higher cost required to translate an investigational new drug to clinical approval. Technological advances in 3D-cell culture models bridge the gap between 2D and in vivo models to improve upon the current success rates of cancer drug discovery.
Areas Covered:
This review focuses on the multicellular tumor spheroid (MCTS), particularly how this model can be utilized for HTS drug discovery. We discuss the current technologies for uniform culture of MCTS suitable for HTS and detection methods utilized for assay development and drug screening.
Expert Opinion:
Substantial hurdles remain before we reach the ultimate goal of robust HTS of large compound libraries with MCTS models. Specifically, we can group these challenges into three categories: MCTS growth, data collection, and data analysis. The MCTS model should be utilized with fluorescent readouts and high-content imaging with a systems biology approach to model human tumors in vitro. Such models will be more predictive of in vivo efficacy, improving on the current success rates of cancer drug discovery from bench to bedside.
Insights
Three-dimensional (3D) multicellular tumor spheroid (MCTS) models offer improved prediction of in vivo efficacy for cancer drug discovery. Overcoming challenges in MCTS culture, data collection, and analysis is key to advancing high-throughput screening (HTS).
Area of Science:
- Oncology
- Drug Discovery
- Biotechnology
Background:
- Traditional 2D cell-based assays have limitations in predicting in vivo cancer drug efficacy.
- This has led to high costs and low success rates in translating new cancer drugs.
- Advances in 3D cell culture models offer a promising alternative.
Purpose of the Study:
- To review the utility of multicellular tumor spheroids (MCTS) for high-throughput screening (HTS) in cancer drug discovery.
- To discuss current technologies for MCTS culture and detection methods for assay development.
- To highlight challenges and future directions for MCTS-based drug screening.
Main Methods:
- Focus on multicellular tumor spheroid (MCTS) models for HTS drug discovery.
- Review of current technologies for uniform MCTS culture.
- Discussion of detection methods for assay development and drug screening.
Main Results:
- MCTS models show potential to bridge the gap between 2D assays and in vivo studies.
- Current technologies enable uniform MCTS culture suitable for HTS.
- Various detection methods can be employed for assay development and drug screening.
Conclusions:
- Hurdles in MCTS growth, data collection, and analysis need to be addressed for robust HTS.
- Integrating fluorescent readouts, high-content imaging, and systems biology approaches is recommended.
- MCTS models, when optimized, can improve the predictive power of preclinical cancer drug discovery.
