Abstract
In vitro tumor models have provided important tools for cancer research and serve as low-cost screening platforms for drug therapies; however, cancer recurrence remains largely unchecked due to metastasis, which is the cause of the majority of cancer-related deaths. The need for an improved understanding of the progression and treatment of cancer has pushed for increased accuracy and physiological relevance of in vitro tumor models. As a result, in vitro tumor models have concurrently increased in complexity and their output parameters further diversified, since these models have progressed beyond simple proliferation, invasion, and cytotoxicity screens and have begun recapitulating critical steps in the metastatic cascade, such as intravasation, extravasation, angiogenesis, matrix remodeling, and tumor cell dormancy. Advances in tumor cell biology, 3D cell culture, tissue engineering, biomaterials, microfabrication, and microfluidics have enabled rapid development of new in vitro tumor models that often incorporate multiple cell types, extracellular matrix materials, and spatial and temporal introduction of soluble factors. Other innovations include the incorporation of perfusable microvessels to simulate the tumor vasculature and model intravasation and extravasation. The drive toward precision medicine has increased interest in adapting in vitro tumor models for patient-specific therapies, clinical management, and assessment of metastatic potential. Here, we review the wide range of current in vitro tumor models and summarize their advantages, disadvantages, and suitability in modeling specific aspects of the metastatic cascade and drug treatment.
Highlights
In vitro and in vivo animal models are important tools in cancer research, enabling the identification of carcinogens, the development of cancer therapies, drug screening, and providing insight into the molecular mechanisms of tumor growth and metastasis
Tumor-microvessel models build on the complexity of avascular microfluidic models by introducing a vessel component and are well suited for modeling tumor–vessel interactions over time and investigating angiogenesis, vessel-induced tumor cell dormancy, intravasation, or extravasation
MK, AP, AW, ZX, and PS reviewed and evaluated the literature and wrote the article
Summary
In vitro and in vivo animal models are important tools in cancer research, enabling the identification of carcinogens, the development of cancer therapies, drug screening, and providing insight into the molecular mechanisms of tumor growth and metastasis. In Vitro Tumor Models to successfully negotiate each of these steps is dependent on the interactions between the cancer cell and the local microenvironment (Wirtz et al, 2011). In vitro models of solid tumors vary in complexity and range from tumor-derived cell lines to 3D models of the tumor microenvironment (Hulkower and Herber, 2011; Wirtz et al, 2011; Infanger et al, 2013; Vidi et al, 2013). Cancer cell lines are easy to grow, allow direct comparison of experimental results, and are widely used to study molecular mechanisms of tumor cell biology (Greshock et al, 2007; Holliday and Speirs, 2011). This review serves as a guide to selection of in vitro platforms best suited to specific applications in tumor biology
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