Liquid-based three-dimensional tumor models for cancer research and drug discovery

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 241; no. 9; pp. 939 - 954
• Main Authors: Ham, Stephanie L, Joshi, Ramila, Thakuri, Pradip S, Tavana, Hossein
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-05-2016
• Subjects: Animals; Antineoplastic Agents - pharmacology; Coculture Techniques - methods; Colorimetry - methods; Drug Discovery - methods; Drug Screening Assays, Antitumor - methods; Fibroblasts; Fluorescence; Humans; Luminescent Measurements - methods; Minireview; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; Spheroids, Cellular; Stromal Cells - pathology; Tumor Microenvironment; anti-cancer drug discovery; tumor microenvironment; cancer stem cells; co-culture spheroids; cancer cell spheroids; 3D tumor models
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/1535370216643772

Tumors are three-dimensional tissues where close contacts between cancer cells, intercellular interactions between cancer and stromal cells, adhesion of cancer cells to the extracellular matrix, and signaling of soluble factors modulate functions of cancer cells and their response to therapeutics. Three-dimensional cultures of cancer cells overcome limitations of traditionally used monolayer cultures and recreate essential characteristics of tumors such as spatial gradients of oxygen, growth factors, and metabolites and presence of necrotic, hypoxic, quiescent, and proliferative cells. As such, three-dimensional tumor models provide a valuable tool for cancer research and oncology drug discovery. Here, we describe different tumor models and primarily focus on a model known as tumor spheroid. We summarize different technologies of spheroid formation, and discuss the use of spheroids to address the influence of stromal fibroblasts and immune cells on cancer cells in tumor microenvironment, study cancer stem cells, and facilitate compound screening in the drug discovery process. We review major techniques for quantification of cellular responses to drugs and discuss challenges ahead to enable broad utility of tumor spheroids in research laboratories, integrate spheroid models into drug development and discovery pipeline, and use primary tumor cells for drug screening studies to realize personalized cancer treatment.