TY - JOUR
T1 - From simplicity to complexity in current melanoma models
AU - Michielon, Elisabetta
AU - de Gruijl, Tanja D.
AU - Gibbs, Susan
N1 - Funding Information: The presented work was funded by the Dutch Government: Rijksdienst voor Ondernemend Nederland, Eurostars program, project number E11275 (IMAGINe project). Publisher Copyright: © 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.
PY - 2022/12
Y1 - 2022/12
N2 - Despite the recent impressive clinical success of immunotherapy against melanoma, development of primary and adaptive resistance against immune checkpoint inhibitors remains a major issue in a large number of treated patients. This highlights the need for melanoma models that replicate the tumor's intricate dynamics in the tumor microenvironment (TME) and associated immune suppression to study possible resistance mechanisms in order to improve current and test novel therapeutics. While two-dimensional melanoma cell cultures have been widely used to perform functional genomics screens in a high-throughput fashion, they are not suitable to answer more complex scientific questions. Melanoma models have also been established in a variety of experimental (humanized) animals. However, due to differences in physiology, such models do not fully represent human melanoma development. Therefore, fully human three-dimensional in vitro models mimicking melanoma cell interactions with the TME are being developed to address this need for more physiologically relevant models. Such models include melanoma organoids, spheroids, and reconstructed human melanoma-in-skin cultures. Still, while major advances have been made to complement and replace animals, these in vitro systems have yet to fully recapitulate human tumor complexity. Lastly, technical advancements have been made in the organ-on-chip field to replicate functions and microstructures of in vivo human tissues and organs. This review summarizes advancements made in understanding and treating melanoma and specifically aims to discuss the progress made towards developing melanoma models, their applications, limitations, and the advances still needed to further facilitate the development of therapeutics.
AB - Despite the recent impressive clinical success of immunotherapy against melanoma, development of primary and adaptive resistance against immune checkpoint inhibitors remains a major issue in a large number of treated patients. This highlights the need for melanoma models that replicate the tumor's intricate dynamics in the tumor microenvironment (TME) and associated immune suppression to study possible resistance mechanisms in order to improve current and test novel therapeutics. While two-dimensional melanoma cell cultures have been widely used to perform functional genomics screens in a high-throughput fashion, they are not suitable to answer more complex scientific questions. Melanoma models have also been established in a variety of experimental (humanized) animals. However, due to differences in physiology, such models do not fully represent human melanoma development. Therefore, fully human three-dimensional in vitro models mimicking melanoma cell interactions with the TME are being developed to address this need for more physiologically relevant models. Such models include melanoma organoids, spheroids, and reconstructed human melanoma-in-skin cultures. Still, while major advances have been made to complement and replace animals, these in vitro systems have yet to fully recapitulate human tumor complexity. Lastly, technical advancements have been made in the organ-on-chip field to replicate functions and microstructures of in vivo human tissues and organs. This review summarizes advancements made in understanding and treating melanoma and specifically aims to discuss the progress made towards developing melanoma models, their applications, limitations, and the advances still needed to further facilitate the development of therapeutics.
KW - animal models
KW - immunotherapy
KW - in vitro models
KW - melanoma
KW - organoids
KW - spheroids
KW - tumor microenvironment
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U2 - https://doi.org/10.1111/exd.14675
DO - https://doi.org/10.1111/exd.14675
M3 - Review article
C2 - 36103206
SN - 0906-6705
VL - 31
SP - 1818
EP - 1836
JO - Experimental dermatology
JF - Experimental dermatology
IS - 12
ER -