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Advances and challenges in human 3D solid tumor models
Naveen R Natesh1, Shyni Varghese1,2,3
1Department of Biomedical Engineering, Duke University, 203 Research Drive, MSRB1 Room No. 381, Durham, NC, 27710 USA.
Abstract:
The field of cancer biology and therapeutics has soared in the past several decades with new therapeutic modalities and options for patients, such as chemoradiotherapy, immunotherapy, and combination therapy. This dramatic success in expanding patient options is primarily attributed to the development of various model systems to elucidate drivers of oncogenesis, tumor maturation and evolution, and response to therapeutics. While mouse models have been a workhorse of cancer research, technological progress in ex vivo patient-derived tumor models has afforded more tunable and scrutable systems for patient-predictive platforms and mechanistic study. This review explores the technological innovations in 3D solid tumor models and their applicability to various aspects of cancer biology and identification of therapeutics. Features of the tumor and tumor microenvironment like spatial heterogeneity, multicellular populations and genomic variations are addressed and elaborated through the establishment of new in vitro models. We further address the integration of perfusable vasculature with 3D tumor models and the potentially wide-ranging applications of these more complex platforms in precision medicine and cancer immunotherapy. Finally, we provide an outlook on the future of experimental cancer models for both biological investigation and bench-to-bedside pipeline development.
Insights
Advancements in 3D patient-derived tumor models offer improved platforms for studying cancer biology and developing new cancer therapeutics. These innovative ex vivo models enhance precision medicine and immunotherapy research.
Area of Science:
- Cancer Biology
- Therapeutics Development
- Translational Oncology
Background:
- Cancer research has advanced significantly due to improved model systems.
- Traditional mouse models are being complemented by sophisticated ex vivo patient-derived tumor models.
- Technological progress enables more tunable and interpretable experimental systems.
Purpose of the Study:
- To review technological innovations in 3D solid tumor models.
- To explore the application of these models in cancer biology and therapeutic identification.
- To discuss the integration of perfusable vasculature into 3D tumor models.
Main Methods:
- Exploration of technological advancements in 3D ex vivo tumor models.
- Analysis of how these models address tumor and microenvironment features like spatial heterogeneity and genomic variations.
- Discussion of integrating perfusable vasculature into complex 3D models.
Main Results:
- 3D patient-derived tumor models provide enhanced platforms for studying oncogenesis, tumor evolution, and therapeutic responses.
- These models allow for the investigation of spatial heterogeneity, multicellular populations, and genomic variations.
- Integration with perfusable vasculature creates more complex platforms for precision medicine and immunotherapy.
Conclusions:
- Innovative 3D tumor models are crucial for advancing cancer biology research.
- These models hold significant potential for developing targeted cancer therapeutics and improving precision medicine.
- Future experimental cancer models will drive both biological discovery and clinical translation.
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