Patton, E ElizabethMueller, Kristen LAdams, David JAnandasabapathy, NiroshanaAplin, Andrew EBertolotto, CorineBosenberg, MarcusCeol, Craig JBurd, Christin EChi, PingHerlyn, MeenhardHolmen, Sheri LKarreth, Florian AKaufman, Charles KKhan, ShaheenKobold, SebastianLeucci, EleonoraLevy, CarmitLombard, David BLund, Amanda WMarie, Kerrie LMarine, Jean-ChristopheMarais, RichardMcMahon, MartinRobles-Espinoza, Carla DanielaRonai, Ze'ev ASamuels, YardenaSoengas, MSVillanueva, JessieWeeraratna, Ashani TWhite, Richard MYeh, IweiZhu, JiyueZon, Leonard IHurlbert, Marc SMerlino, Glenn2024-10-292024-10-292021-05-10Cancer Cell . 2021 May 10;39(5):610-631https://hdl.handle.net/20.500.12105/25366we are grateful to the Melanoma Research Alliance for funding the Melanoma Models Workshop 2020 (Washington, DC, USA) that enabled the authors to discuss and prepare the manuscript. The authors thank Nancy R. Gough (BioSerendipity) for assistance with drafting the manuscript and Ray Gustin (MRA Patient Advocate) for discussions and note preparations. This work was supported by funding from the Intramural Research Program, National Institutes of Health, the National Cancer Institute (R13CA250294), Pigment Cell and Melanoma Research (Wiley) and Disease Models and Mechanisms (Company of Biologists). D.J.A. is supported by Cancer Research UK and the Wellcome Trust. N.A. is supported by the National Institute of Arthritis and Musculoskeletal and Skin Disease R01 AR070234. A.E.A. is supported by grants R01 CA182635, R01 CA196278, R01 CA253977, and P01 CA114046 from the National Institutes of Health/National Cancer Institute and by The Helman Family-Melanoma Research Alliance Team Science award (#559058). C.B. is supported by INCa (grant INCa_10573) and Le Fonds dedotation de La Societe Francaise de Dermatologie. M.B. is supported by NIH/NCI grants (P50 CA121974, U01 CA238728, U01 CA233096, P30 CA016359, P01 CA128814, P01 CA206980, R01 CA244660, R01 CA216101, R01 CA212376, R01 CA204002, R01 CA216846, R01 CA196566, and R01 CA196660). C.E.B. is supported by National Institutes of Health R01CA237213. C.J.C. is supported by DOD CDMRP: W81XWH2010288. P.C. is supported by NIH/NCI grants (R01 CA228216, DP2 CA174499, P50 CA217694), Cycle for Survival Fund, and Geoffrey Beene Cancer Research Fund. M.H. is supported by NIH grants R01 CA238237, U54 CA224070, P01 CA114046, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. S.L.H. is supported by grants from the National Institutes of Health (R01 CA121118), the Leveraged Finance Fights MelanomaMelanoma Research Alliance Established Investigator award, and the Huntsman Cancer Foundation. F.A.K. is supported by NIH/NCI K22CA197058, NIH/NCI R03CA227349, Melanoma Research Alliance Young Investigator award, MRF Mucosal Melanoma Career Development award, and Harry J. Lloyd Charitable Trust Career Development award. C.K.K. is supported by NIH R01CA240633 and Melanoma Research Alliance Young Investigator award. S. Khan is supported by Melanoma Research Alliance-Society for Immunotherapy of Cancer Young Investigator award in Immune-Related Adverse Events. S. Kobold is supported by the Marie-Sklodowska-Curie Program Training Network for Optimizing Adoptive T Cell Therapy of Cancer funded by the H2020 Program of the European Union (grant 955575), the Heritage Foundation, the International Doctoral Program i-Target: Immunotargeting of Cancer funded by the Elite Network of Bavaria, the Bristol Myers SquibbMelanoma Research Alliance Young Investigator award, the Ernst-Jung-Stiftung, the Bundesministerium fur Bildung und Forschung Project Oncoattract, the European Research Council grant 756017, ARMOR-T, the German Research Foundation, the Fritz Bender Foundation, and the Jose -Carreras Foundation. E.L. is supported by the Amanda and Jonatan Eilian-Melanoma Research Alliance Young Investigator award, Belgian Federation for Cancer, Kom op tegen Kanker, and is a member of the EurOPDX Consortium and receives funding from the European Union's Horizon 2020 research and innovation programme (EDIReX grant, no.731105, www.europdx.eu).C.L.is supported by Saban Family Foundation-Melanoma Research Alliance Team Science award (402792). D.B.L. is supported by NIH: R01GM101171 and R21ES032305: DOD: CA190267, CA170628, and NF170044. A.W.L. is funded by NIH NCI R01CA238163, Cancer Research Institute Lloyd J. Old STAR award, The Mark Foundation for Cancer Research Emerging Leader award, and American Cancer Society RSG-18-169-01-LIB. K.L.M. is supported by the NCI Intramural Research Program of the NIH, and in part by NCI Director's Innovation award. J.-C.M. is supported by FWO (#G.0929.16N), Stichting Tegen Kanker, Melanoma Research Alliance-Established Investigator award (#623591), and KU Leuven (C1 grant). R.M. is supported by Cancer Research UK (A27412, A22902, and C5759/A29061), Wellcome Trust (100282/Z/12/Z), European Research Council Advanced grant (ERC-ADG-2014 671262), and the European Commission (Horizon 2020 program: UM Cure; project no. 667787). M.M. is supported by the National Cancer Institute, CA176839 & CA042014. E.E.P. is supported by MRC HGU Program (MC_UU_00007/9), ERC (ZF-MEL-CHEMBIO-648489), and the Anna-Maria and Stephen Kellen Foundation-Melanoma Research Alliance Team Science award (#687306). C.D.R.-E. is supported by MRC(MR/S01473X/1), Consejo Nacional de Ciencia y Tecnologia of Mexico (Projects A3-S-31603 and A1-S-30165), Programa de Apoyo a Proyectos de Investigacio n e Innovacio n Tecnologica (PAPIIT UNAM) (IA202020), Academy of Medical Sciences Newton Advanced Fellowship (NAF/R2/180782), and by a Wellcome Sanger Institute International Fellowship. Z.A.R. is supported by NCI CA197465 and NCI CA128814. M.S.S. is supported by grants from the Spanish Ministry of Economy and Innovation (SAF2017-89533-R), the Sokoloff Family-Melanoma Research Alliance-Established Investigator award, and by grants from the and Fundacion ``La Caixa and the Asociacion Espanola Contra el Cancer'' (AECC). Y.S. is supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 770854), and the Melanoma Research Alliance-Established Investigator award (#622106). J.V. is supported by P01 CA114046, R01 CA215733, R01 CA226888, P30 CA010815, DoD W81XWH2010356, and PA Department of Health. A.T.W. is supported by R01CA207935, P01 CA114046, R01 CA2322456, a Melanoma Research Alliance Team Science award, a Bloomberg Distinguished Professorship, and the E.V. McCollum Endowed Chair. R.M.W. is supported by the Anna-Maria and Stephen Kellen Foundation-Melanoma Research Alliance Team Science award, NIH Research Program grant R01CA229215, NIH Director's New Innovator award DP2CA186572, NIH R01CA238317, NIH R01CA229215, The Pershing Square Sohn Foundation, American Cancer Society, The Alan and Sandra Gerry Metastasis Research Initiative at the Memorial Sloan Kettering Cancer Center, The Harry J. Lloyd Foundation, Consano, and the Starr Cancer Consortium. I.Y. is supported by NCI: R37CA240914, The Black Family-Melanoma Research Alliance Team Science award in Acral Melanoma, and Dermatology Foundation Stiefel Scholar award in Skin Cancer. J.Z. is supported by Melanoma Research Alliance Acral Melanoma Team Science award #579152 and NIH grant R01GM071725. L.I.Z. is supported by Cancer Biology R01 CA103846, NIH Melanoma PPG, P01CA63222, Melanoma Research Alliance-Established Investigator award, and Starr Cancer Consortium grant. G.M. is funded by the NIH Intramural Research Program. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors read and contributed to the manuscript. Wewish to apologize to the authors of substantive melanoma model studies that could not be cited or discussed here due to limitations in size and scope.There is a lack of appropriate melanoma models that can be used to evaluate the efficacy of novel therapeutic modalities. Here, we discuss the current state of the art of melanoma models including genetically engineered mouse, patient-derived xenograft, zebrafish, and ex vivo and in vitro models. We also identify five major challenges that can be addressed using such models, including metastasis and tumor dormancy, drug resistance, the melanoma immune response, and the impact of aging and environmental exposures on melanoma progression and drug resistance. Additionally, we discuss the opportunity for building models for rare subtypes of melanomas, which represent an unmet critical need. Finally, we identify key recommendations for melanoma models that may improve accuracy of preclinical testing and predict efficacy in clinical trials, to help usher in the next generation of melanoma therapies.engVoRhttp://creativecommons.org/licenses/by/4.0/animal modelsdrug discoveryimmunotherapymelanomatargeted therapytherapeuticstumor microenvironmentAttribution 4.0 International33545064395610-631https://pmc.ncbi.nlm.nih.gov/articles/PMC8378471/pdf/nihms-1689188.pdfopen access