Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 175, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.addr.2021.04.001
Keywords
3D models; hydrogel-based ECM; Drug screening; Tumor-stromal cell interactions; Immunotherapy
Categories
Funding
- European Research Council (ERC) Consolidator Grant [617445-PolyDorm]
- ERC Advanced Grant [835227-3DBrainStrom]
- ERC Proof of Concept (PoC) Grant [862580-3DCanPredict]
- Israel Science Foundation [1969/18]
- Melanoma Research Alliance [615808]
- Israel Cancer Research Fund (ICRF) Professorship award [PROF-18-682]
- Israel Cancer Association (ICA) USA [20150909]
- Morris Kahn Foundation
- Israeli Ministry of Health
- Fundacao para a Ciencia e Tecnologia-Ministerio da Ciencia, Tecnologia e Ensino Superior (FCT-MCTES) [ENMed/0051/2016]
- la Caixa Foundation [LCF/PR/HR19/52160021, CF01-00014]
- Naomi Foundation
- Rothschild Foundation (IL)
- Fundação para a Ciência e a Tecnologia [ENMed/0051/2016] Funding Source: FCT
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Three-dimensional cancer models have been developed to study a wide range of biological applications, including cell signaling pathways, metastatic cascade steps, and personalized medicine, in vitro. By combining different cell types and external stimuli, these models can more accurately mimic the biology and pathophysiology of in vivo tumors.
The complexity and diversity of the biochemical processes that occur during tumorigenesis and metastasis are frequently over-simplified in the traditional in vitro cell cultures. Two-dimensional cultures limit researchers' experimental observations and frequently give rise to misleading and contradictory results. Therefore, in order to overcome the limitations of in vitro studies and bridge the translational gap to in vivo applications, 3D models of cancer were developed in the last decades. The three dimensions of the tumor, including its cellular and extracellular microenvironment, are recreated by combining co cultures of cancer and stromal cells in 3D hydrogel-based growth factors-inclusive scaffolds. More complex 3D cultures, containing functional blood vasculature, can integrate in the system external stimuli (e.g. oxygen and nutrient deprivation, cytokines, growth factors) along with drugs, or other therapeutic compounds. In this scenario, cell signaling pathways, metastatic cascade steps, cell differentiation and self-renewal, tumor-microenvironment interactions, and precision and personalized medicine, are among the wide range of biological applications that can be studied. Here, we discuss a broad variety of strategies exploited by scientists to create in vitro 3D cancer models that resemble as much as possible the biology and patho-physiology of in vivo tumors and predict faithfully the treatment outcome. (c) 2021 Elsevier B.V. All rights reserved.
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