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Updated: Feb 24, 2026
Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening
Published on: September 5, 2018
Three- and Four-Dimensional Spheroid and FiSS Tumoroid Cultures: Platforms for Drug Discovery and Development and
1Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Departments of Internal Medicine, University of South Florida, Tampa, FL 33612, USA; Transgenex Nanobiotech Inc., Tampa, FL 33612, USA.
Abstract:
There have been remarkable improvements in our understanding of cancer biology. However, therapeutic improvements, with a few exceptions, have been minimal. Also, significant challenges remain in translating fundamental discoveries in cancer biology and genetics into effective drugs and cures. Traditional two-dimensional monolayer cell cultures lack predictive value, resulting in a >90% failure rate of compounds in clinical trials. A developing cancer is a symbiotic tissue consisting of cancer cells, including cancer stem cells (CSCs), and cohabitating with the components of its environment to form a tumor microenvironment (TME) niche. Throughout the process of tumorigenesis, ubiquitous autocrine and paracrine signaling between the cellular and noncellular components of the TME dictates the milieu and structure of this niche. Arising out of such interactions are the cancer cell's phenotypic characteristics, such as stemness, epithelial mesenchymal transformation (EMT), and drug resistance which in turn greatly affect the response of these cells to drug therapy. For these reasons, in order to delineate the mechanism of tumorigenesis and in the process discover drugs that will have greatest impact on tumor growth, it becomes imperative to study the cancer cell in context of its microenvironment. In the present review, we enumerate the advantages of three- and four-dimensional (3D and 4D) cell cultures and describe the various cell culture platforms that are being used to study tumorigenesis in vitro. These culture systems will not only aid in the study of tumor progression complexities in a cost-effective and rapid manner; they also are expected to facilitate the discovery and delivery of therapeutic regimens that will have more success making it to the clinic.
Insights
Traditional cell cultures fail to predict drug efficacy. Advanced 3D and 4D cell cultures better model the tumor microenvironment (TME), aiding cancer stem cell (CSC) research and improving drug discovery for cancer therapy.
Area of Science:
- Oncology
- Biotechnology
- Cell Biology
Background:
- Cancer biology understanding has advanced, yet therapeutic progress remains limited.
- Translating discoveries into effective cancer drugs faces significant challenges.
- Traditional 2D cell cultures have low predictive value, leading to high clinical trial failure rates (>90%).
Purpose of the Study:
- To review the advantages of 3D and 4D cell cultures for studying tumorigenesis.
- To describe current cell culture platforms for in vitro tumor microenvironment (TME) research.
- To highlight how advanced cultures can improve cancer drug discovery and clinical translation.
Main Methods:
- Review of existing literature on 3D and 4D cell culture techniques.
- Analysis of cell culture platforms used to model the tumor microenvironment (TME).
- Discussion of how these models simulate cancer cell-TME interactions, including cancer stem cells (CSCs) and EMT.
Main Results:
- 3D and 4D cell cultures offer superior recapitulation of the TME compared to 2D cultures.
- These advanced models facilitate the study of complex tumorigenesis mechanisms.
- They provide a more accurate platform for evaluating drug responses and resistance.
Conclusions:
- Studying cancer cells within their microenvironment is crucial for understanding tumorigenesis and developing effective therapies.
- Advanced cell culture systems (3D/4D) are essential for overcoming limitations of traditional methods.
- These innovative platforms promise to accelerate the discovery and clinical success of novel cancer therapeutics.
