TY - JOUR
T1 - The Applications and Challenges of the Development of In Vitro Tumor Microenvironment Chips
AU - Johnson, Annika
AU - Reimer, Samuel
AU - Childres, Ryan
AU - Cupp, Grace
AU - Kohs, Tia C.L.
AU - McCarty, Owen J.T.
AU - Kang, Youngbok (Abraham)
N1 - Publisher Copyright:
© 2022, The Author(s) under exclusive licence to Biomedical Engineering Society.
PY - 2023/2
Y1 - 2023/2
N2 - The tumor microenvironment (TME) plays a critical, yet mechanistically elusive role in tumor development and progression, as well as drug resistance. To better understand the pathophysiology of the complex TME, a reductionist approach has been employed to create in vitro microfluidic models called “tumor chips”. Herein, we review the fabrication processes, applications, and limitations of the tumor chips currently under development for use in cancer research. Tumor chips afford capabilities for real-time observation, precise control of microenvironment factors (e.g. stromal and cellular components), and application of physiologically relevant fluid shear stresses and perturbations. Applications for tumor chips include drug screening and toxicity testing, assessment of drug delivery modalities, and studies of transport and interactions of immune cells and circulating tumor cells with primary tumor sites. The utility of tumor chips is currently limited by the ability to recapitulate the nuances of tumor physiology, including extracellular matrix composition and stiffness, heterogeneity of cellular components, hypoxic gradients, and inclusion of blood cells and the coagulome in the blood microenvironment. Overcoming these challenges and improving the physiological relevance of in vitro tumor models could provide powerful testing platforms in cancer research and decrease the need for animal and clinical studies.
AB - The tumor microenvironment (TME) plays a critical, yet mechanistically elusive role in tumor development and progression, as well as drug resistance. To better understand the pathophysiology of the complex TME, a reductionist approach has been employed to create in vitro microfluidic models called “tumor chips”. Herein, we review the fabrication processes, applications, and limitations of the tumor chips currently under development for use in cancer research. Tumor chips afford capabilities for real-time observation, precise control of microenvironment factors (e.g. stromal and cellular components), and application of physiologically relevant fluid shear stresses and perturbations. Applications for tumor chips include drug screening and toxicity testing, assessment of drug delivery modalities, and studies of transport and interactions of immune cells and circulating tumor cells with primary tumor sites. The utility of tumor chips is currently limited by the ability to recapitulate the nuances of tumor physiology, including extracellular matrix composition and stiffness, heterogeneity of cellular components, hypoxic gradients, and inclusion of blood cells and the coagulome in the blood microenvironment. Overcoming these challenges and improving the physiological relevance of in vitro tumor models could provide powerful testing platforms in cancer research and decrease the need for animal and clinical studies.
KW - Cancer research
KW - Microfluidic device
KW - Tumor chip
KW - Tumor microenvironment (TME)
KW - Tumor model
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U2 - 10.1007/s12195-022-00755-7
DO - 10.1007/s12195-022-00755-7
M3 - Review article
AN - SCOPUS:85144909175
SN - 1865-5025
VL - 16
SP - 3
EP - 21
JO - Cellular and Molecular Bioengineering
JF - Cellular and Molecular Bioengineering
IS - 1
ER -