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Updated: May 3, 2026

Generation of 3D Tumor Spheroids for Drug Evaluation Studies
Published on: February 24, 2023
Physiologically relevant 3D tumor models for therapeutic screening
Renjian Xie1, Jianqiong Yang1, Xiaolu Lu1
1Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Disease (Ministry of Education), School of Medical and Information Engineering, Gannan Medical University, Ganzhou, Jiangxi, 341000, China; Jiangxi Provincial Key Laboratory of Tissue Engineering, Gannan Medical University, Ganzhou, Jiangxi, 341000, China.
Abstract:
The heterogeneity of the tumor microenvironment poses a significant challenge to the success of anti-cancer therapeutics. Consequently, there is an urgent need to generate comprehensive data to elucidate the mechanisms underlying tumor resistance and to inform the rational and systematic application of anti-cancer drugs to mitigate drug resistance. In-vitro tumor models based on established cell lines are widely employed in studying the mechanisms of action of drugs; however, these traditional models often fail to accurately recapitulate the complexity of native tumors, particularly in terms of the heterogenous and intricate tumor microenvironment, including cellular composition, intercellular communication, and interactions between cells and extracellular matrix. As a result, preclinical data often diverges from clinical outcomes. In recent years, the emergence of patient-derived three-dimensional (3D) models including spheroids, organoids, tumor-on-a-chip systems, and 3D bioprinting has offered promising alternatives for addressing these limitations and enhancing the predictive power of tumor drug screening. In this review, we explore the relationship between the complexity of the tumor microenvironment, tumor drug resistance, and then introduce the current biofabrication techniques enabling the reconstruction of 3D tumor models in vitro. We delve deeper into a myriad of applications of such models for a wide range of cancer indications. These models offer a morfailures andlly relevant platform for evaluating anti-cancer drugs with the potential to improve translational accuracy, reduce drug development failures, and accelerate the discovery of cancer therapies.
Insights
Patient-derived 3D tumor models offer a more accurate preclinical platform. These advanced models improve anti-cancer drug screening, reduce development failures, and accelerate cancer therapy discovery.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- Tumor microenvironment heterogeneity challenges anti-cancer drug efficacy.
- Traditional in vitro models fail to replicate native tumor complexity, leading to poor clinical translation.
- There is a critical need for advanced models to understand and overcome tumor drug resistance.
Purpose of the Study:
- To review the link between tumor microenvironment complexity and drug resistance.
- To introduce biofabrication techniques for creating advanced 3D tumor models.
- To explore the applications of these models in cancer research and drug development.
Main Methods:
- Review of current literature on tumor microenvironment, drug resistance, and 3D tumor models.
- Discussion of biofabrication techniques including spheroids, organoids, tumor-on-a-chip, and 3D bioprinting.
- Exploration of applications across various cancer indications.
Main Results:
- Patient-derived 3D models (spheroids, organoids, tumor-on-a-chip, 3D bioprinting) better mimic tumor complexity.
- These advanced models enhance the predictive power of anti-cancer drug screening.
- 3D models show potential for improving translational accuracy and reducing drug development failures.
Conclusions:
- Advanced 3D tumor models are crucial for understanding drug resistance.
- Biofabrication techniques enable the creation of more physiologically relevant in vitro tumor models.
- These models promise to accelerate the discovery and development of effective cancer therapies.

