Cell culture and in vitro models are the cornerstone of cancer research, relying on a plethora of cell lines developed from various cancers. These models serve as a crucial first step in preclinical research for quick screening and drug testing. Cells in vitro are evenly spread, have optimal access to media, metabolites, or compounds, and show good responses to treatment. However, when these drugs are applied to animal models, they often fail due to various factors, including cell morphology, cell-cell contacts, microenvironment, or immunity. Recent studies have shown that 3D in vitro models can better replicate these features, providing a more accurate model for cancer studies. Despite these advancements, there remains a significant gap in understanding the full potential and limitations of 3D in vitro models, necessitating further investigation and validation.

This Research Topic aims to demonstrate the advantages of 3D in vitro models compared to traditional 2D cell culture models. Many cancers can be modeled at various levels of complexity, using both immortalized cell lines or patient material/primary cultures. The goal of this Research Topic is to collect diverse examples of applicable research in 3D in vitro models, which could contribute to the 3R principle in using animal models—reduce, replace, refine—as research done on such 3D systems more closely resembles in vivo conditions. By addressing these aims, the research hopes to answer critical questions about the efficacy, reliability, and broader applications of 3D in vitro models in cancer research.

To gather further insights into the range and limitations of 3D in vitro models in cancer research, we welcome articles addressing, but not limited to, the following themes:

- Comparison of cells grown in 2D versus 3D conditions
- Basic mechanisms of cell biology in 3D models
- Investigation of stemness, differentiation, and resistance in 3D cultures
- Preclinical drug testing using 3D in vitro models
- Physiological and pathological processes in 3D systems
- Development and application of spheroids, organoids, and tumoroids
- In vitro organogenesis and its implications for cancer research

By exploring these themes, the research aims to provide a comprehensive understanding of the potential and challenges associated with 3D in vitro models in cancer research. Please note, review papers should be citing as many original research papers as possible, and not other review papers.

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Frontiers in Genetics

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