From 2D to 3D and beyond: the evolution and impact of in vitro tumor models in cancer research
Top Cited Papers
- 25 July 2025
- journal article
- review article
- Published by Springer Nature in Nature Methods
- Vol. 22 (9) , 1776-1787
Abstract
In vitro tumor models are essential tools for cancer research, offering key insights into not only tumor biology but also therapeutic responses. The transition from traditional two-dimensional to three-dimensional organoid systems marks a paradigm shift in cancer modeling. Although two-dimensional models have been instrumental in elucidating fundamental molecular and genetic mechanisms, they fail to accurately replicate the intricate three-dimensional architecture and dynamic microenvironment characteristic of human tumors. Here we outline how advanced organoid technologies now enable more faithful recapitulation of tumor heterogeneity that better mimic native tissue mechanics and biochemistry. We discuss emerging methods, including air-liquid interface cultures, microfluidic tumor-on-a-chip devices and high-content imaging integrated with machine learning, which collectively address longstanding challenges such as matrix variability and the limited incorporation of immune and vascular elements. These innovations promise to enhance reproducibility and scalability while providing unprecedented insights into tumor biology, cancer progression and therapeutic strategies.Keywords
Funding Information
- Find The Cause Breast Cancer Foundation
This publication has 170 references indexed in Scilit:
- Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membraneDevelopment, 1989
- GLUCOSE DIFFUSIVITY IN MULTICELLULAR TUMOR SPHEROIDS1988
- Cell and Environment Interactions in Tumor Microregions: The Multicell Spheroid ModelScience, 1988
- The molecular fibrillar structure of collagen and its relationship to the mechanical properties of connective tissueBiophysical Chemistry, 1988
- Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells.Proceedings of the National Academy of Sciences, 1987
- Basement membrane complexes with biological activityBiochemistry, 1986
- Long-term human breast carcinoma cell lines of metastatic origin: Preliminary characterizationIn Vitro Cellular & Developmental Biology - Plant, 1978
- Radiation response of multicell spheroids--an in vitro tumour model.1976
- Breast Tumor Cell Lines From Pleural Effusions2JNCI: Journal of the National Cancer Institute, 1974
- A Human Cell Line From a Pleural Effusion Derived From a Breast Carcinoma 2JNCI: Journal of the National Cancer Institute, 1973