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.
- Patton, E. E.
- Mueller, K. L.
- Adams, D. J.
- Anandasabapathy, N.
- Aplin, A. E.
- Bertolotto, C.
- Bosenberg, M.
- Ceol, C. J.
- Chi, P.
- Herlyn, M.
- Holmen, S. L.
- Karreth, F. A.
- Kaufman, C. K.
- Khan, S.
- Kobold, S.
- Leucci, E.
- Levy, C.
- Lombard, D. B.
- Lund, A. W.
- Marie, K. L.
- Marine, J. C.
- Marais, R.
- McMahon, M.
- Robles-Espinoza, C. D.
- Ronai, Z. A.
- Samuels, Y.
- Soengas, M. S.
- Villanueva, J.
- Weeraratna, A. T.
- White, R. M.
- Yeh, I.
- Zhu, J.
- Zon, L. I.
- Hurlbert, M. S.
- Merlino, G.
Keywords
- animal models
- drug discovery
- immunotherapy
- melanoma
- targeted therapy
- therapeutics
- tumor microenvironment
- grant support from AstraZeneca and OpenTargets. N.A. is a consultant for Viela Bio.
- A.E.A. reports receiving a commercial research grant from Pfizer. (2013–2017) and
- has ownership interest in patent number 9880150. M.B. is a consultant for Eli Lilly
- and Company and Bristol-Myers Squibb. P.C. received grants and personal fees from
- Deciphera, personal fees from Exelixis, grants from Array/Pfizer, and personal fees
- from Zai lab. S. Khan has a US patent pending (62/654,025). S. Kobold received
- research support from TCR2 Inc and Arcus Bioscience for work unrelated to this
- manuscript, has licensed IP to TCR2 Inc, has received consultancy fees from TCR2 Inc
- and Novartis, and is an inventor of several patents and patent applications in the
- field of cancer immunotherapy. R.M. consults for Pfizer, and as a former employee of
- the Institute of Cancer Research he may benefit financially from drug-discovery
- programs that are commercialized. M.M. receives research funding from Pfizer and
- Deciphera Pharma
- serves as a scientific advisor to Pfizer, Deciphera Pharma,
- Revolution Medicine, and ARO
- and receives royalty income from the University of
- California for Braf(CA) mice, which are the basis of several GEM models of
- BRAF(V600E)-driven melanoma described in this review. Z.A.R. is founder and
- scientific advisor of Pangea Therapeutics. Y.S. is a consultant of Achilles
- Therapeutics Limited. A.T.W. sits on the advisory board for Melanoma Research
- Foundation, Phoremost Technologies, and Healthe Scientific. R.M.W. is a paid
- consultant to N-of-One Therapeutics, a subsidiary of Qiagen
- is on the Scientific
- Advisory Board of Consano but receives no income for this
- and receives royalty
- payments for the use of the casper line from Carolina Biologicals. L.I.Z. is a
- founder and stockholder of Fate Therapeutics, CAMP4 Therapeutics, and Scholar Rock,
- and a consultant for Celularity.
