Application of In vitro Reconstructed 3D Biomimetic Tumor Microenvironment Models in Cancer Research

Yinuo Ma; Zhiyuan Lu; Yili Sun; Jia Li

doi:10.29328/journal.acst.1001051

Abstract

Research Article

Application of In vitro Reconstructed 3D Biomimetic Tumor Microenvironment Models in Cancer Research

Yinuo Ma, Zhiyuan Lu, Yili Sun and Jia Li

Published: 08 June, 2026 | Volume 10 - Issue 1 | Pages: 16-27

Cancer is a highly heterogeneous and dynamic disease whose progression, metastasis, therapeutic resistance, and immune escape are strongly regulated by the tumor microenvironment (TME). However, conventional two-dimensional (2D) cell culture systems and animal models often fail to recapitulate the structural organization, multicellular interactions, biochemical gradients, and mechanical properties of native tumors, thereby limiting the translational efficiency of preclinical cancer research and drug development. In recent years, in vitro three-dimensional (3D) biomimetic tumor models-including tumor spheroids, tumor organoids, and tumor-on-a-chip systems—have emerged as powerful platforms for reconstructing physiologically relevant tumor microenvironments and investigating complex tumor behaviors.
In this review, we systematically summarize the construction principles, biological characteristics, advantages, and limitations of major 3D biomimetic tumor models. We further discuss their recent applications in drug screening, precision medicine, tumor heterogeneity research, cancer stem cell investigation, metastasis, therapeutic resistance, and immunotherapy evaluation. Particular emphasis is placed on the comparative advantages of different 3D systems in modeling dynamic tumor–microenvironment interactions and supporting translational oncology research. Additionally, we will discuss the current problems of vascularisation, extracellular matrix biomimetics, experimental reproducibility, standardisation, and large-scale clinical translation. Finally, we present some new directions for future work, including three-dimensional bioprinting, multi-omics technology, artificial intelligence, and multi-organ-on-a-chip platforms, which may further improve the physiological relevance and predictive power of next-generation tumor models.
In short, this review has listed the current progress of 3D biomimetic tumour modelling and discussed some prospects for its use in mechanistic studies of cancer, drug discovery, etc.

Read Full Article HTML DOI: 10.29328/journal.acst.1001051 Cite this Article Read Full Article PDF

Keywords:
Tumor microenvironment; 3D biomimetic tumor models; Tumor spheroids; Tumor organoids; Tumor-on-a-chip; Precision oncology

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University of Agriculture, Pakistan

Muhammad Sarwar Khan

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University of Jacqmar, Inc., USA

John St. Cyr

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College of Fisheries, CAU(I), Tripura, India

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Assaf Harofeh Medical Center, Israel

Leonid Feldman

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University of Tubingen, Germany

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Eastern Mediterranean University, Cyprus

Zehra Guchan TOPCU

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Russia

Victor V Apollonov

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India

Rohit Kulshrestha

University of Port Harcourt Teaching Hospital, Nigeria

Dr. Elizabeth A Awoyesuku

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NC A&T State University, USA

Moran Sciamama-Saghiv

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Ido-Ekiti/Afe Babalola University, Nigeria

Dr. Shuaib Kayode Aremu

Ekiti State University, Nigeria

Adebukola Ajite

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Wollo University, Ethiopia

Atsedemariam Andualem

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Ivano- Frankivsk National Medical University, Ukraine

Nataliya Kitsera

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Diaverum: PADC, Jeddah, Saudi Arabia

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Department of Biotechnology, Uttaranchal college of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India

Archna Dhasmana

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Helen Figge

Ph.D, Boston University Department of Communication Sciences and Disorders and Knowledge Research Institute, Inc., 2131 Reflection Bay Drive, Arlington, Texas 76013, USA