Melanoma models for the next generation of therapies

E. Elizabeth Patton; Kristen L. Mueller; David J. Adams; Niroshana Anandasabapathy; Andrew E. Aplin; Corine Bertolotto; Marcus Bosenberg; Craig J. Ceol; Christin E. Burd; Ping Chi; Meenhard Herlyn; Sheri L. Holmen; Florian A. Karreth; Charles K. Kaufman; Shaheen Khan; Sebastian Kobold; Eleonora Leucci; Carmit Levy; David B. Lombard; Amanda W. Lund; Kerrie L. Marie; Jean Christophe Marine; Richard Marais; Martin McMahon; Carla Daniela Robles-Espinoza; Ze'ev A. Ronai; Yardena Samuels; Maria S. Soengas; Jessie Villanueva; Ashani T. Weeraratna; Richard M. White; Iwei Yeh; Jiyue Zhu; Leonard I. Zon; Marc S. Hurlbert; Glenn Merlino

doi:10.1016/j.ccell.2021.01.011

Melanoma models for the next generation of therapies

E. Elizabeth Patton^*, Kristen L. Mueller^*, David J. Adams, Niroshana Anandasabapathy, Andrew E. Aplin, Corine Bertolotto, Marcus Bosenberg, Craig J. Ceol, Christin E. Burd, Ping Chi, Meenhard Herlyn, Sheri L. Holmen, Florian A. Karreth, Charles K. Kaufman, Shaheen Khan, Sebastian Kobold, Eleonora Leucci, Carmit Levy, David B. Lombard, Amanda W. LundKerrie L. Marie, Jean Christophe Marine, Richard Marais, Martin McMahon, Carla Daniela Robles-Espinoza, Ze'ev A. Ronai, Yardena Samuels, Maria S. Soengas, Jessie Villanueva, Ashani T. Weeraratna, Richard M. White, Iwei Yeh, Jiyue Zhu, Leonard I. Zon, Marc S. Hurlbert, Glenn Merlino^*

^*Corresponding author for this work

Human Molecular Genetics Biochemistry

Research output: Contribution to journal › Review article › peer-review

118 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	610-631
Number of pages	22
Journal	Cancer Cell
Volume	39
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2021.01.011
State	Published - 10 May 2021

Funding

Funders	Funder number
“la Caixa” Foundation
Ernst-Jung-Stiftung
Carreras Foundation
Bundesministerium für Bildung und Forschung Project Oncoattract
Melanoma Research Alliance
Carolina Biologicals
Fritz-Bender-Stiftung
Consejo Nacional de Ciencia y Tecnolog?a of Mexico
Dermatology Foundation
Le Fonds de dotation de La Société Française de Dermatologie
Alan and Sandra Gerry Metastasis Research Initiative
Fate Therapeutics
Pershing Square Foundation
Albert Einstein Cancer Center
Bristol Myers Squibb-Melanoma Research Alliance
Fonds Wetenschappelijk Onderzoek
Sokoloff Family-Melanoma Research Alliance-Established
Melanoma Research Alliance-Society
Amanda and Jonatan Eilian-Melanoma Research Alliance
National Institutes of Health
Deutsche Forschungsgemeinschaft
ARMOR-T
European Commission
Cancer Research UK
Pigment Cell and Melanoma Research
José-Carreras Foundation
Mark Foundation For Cancer Research
Director's New Innovator award
Heritage Foundation
Wellcome Sanger Institute
Army Research Office
EDIReX
Institute of Cancer Research
Pangea Therapeutics
Intramural Research Program
Director's Innovation award
MRF Mucosal Melanoma
Fundaci?n ?
Harry J. Lloyd Foundation
AstraZeneca
Camp4 Therapeutics
Leveraged Finance Fights Melanoma-Melanoma Research Alliance
Stichting Tegen Kanker
Horizon 2020
Medical Research Council	MR/S01473X/1
National Cancer Institute	P50CA217694, P01CA128814, R37CA240914, R01CA196566, DP2CA186572, U01CA233096, R01CA216101, R01CA196660, R01CA232246, R01CA212376, R01CA240633, R01CA237213, R01CA215733, R01CA216846, U01CA238728, R01CA238163, R35CA197465, R13CA250294, R01CA226888, P30CA042014, R01CA229215, R01CA228216, R01CA121118, P01CA206980, R01CA253977, R01CA244660, R01CA207935, R01CA232256, R01CA103846, P30CA016359, R01CA196278, ZIABC011167, R01CA238317, R03CA227349, R01CA238237, P01CA114046, R01CA182635, P50CA121974, P30CA008748, K22CA197058, DP2CA174499, P30CA010815, R01CA176839, U54CA224070, R01CA204002
National Institute of General Medical Sciences	R01GM071725, R01GM101171
National Institute of Environmental Health Sciences	R21ES032305
U.S. Department of Defense	CA190267, NF170044, CA170628
Melanoma Research Alliance Acral Melanoma Team Science	R01GM071725, 579152
Pfizer	9880150
Saban Family Foundation-Melanoma Research Alliance Team Science	R01GM101171, 402792, R21ES032305
American Cancer Society	RSG-18-169-01-LIB
Starr Cancer Consortium	R37CA240914
Horizon 2020 Framework Programme	731105, 671262, 770854
University of California for Braf	V600E
Academy of Medical Sciences Newton	NAF/R2/180782
Exelixis	62/654,025
NIH NCI	R01CA238163
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation	R01 CA121118
Huntsman Cancer Foundation	K22CA197058, R03CA227349
Harry J. Lloyd Charitable Trust	R01CA240633
Helman Family-Melanoma Research Alliance Team Science	559058, INCa_10573
Spanish Ministry of Economy and Innovation	SAF2017-89533-R
Melanoma Research	623591
Wellcome Trust	100282
KU Leuven	100282/Z/12/Z, A22902, A27412, ERC-ADG-2014 671262, C5759/A29061
Melanoma Research Alliance-Established	P30 CA010815, W81XWH2010356, R01CA207935, R01 CA226888, R01 CA215733, 622106, R01 CA2322456
UM Cure	CA042014, 667787
Anna-Maria and Stephen Kellen Foundation-Melanoma Research Alliance Team Science	687306
National Institute of Arthritis and Musculoskeletal and Skin Diseases	R01AR070234
MRC HGU	MC_UU_00007/9, ZF-MEL-CHEMBIO-648489
McCollum Endowed Chair	DP2CA186572, R01CA238317, R01CA229215
DoD CDMRP	DP2 CA174499, W81XWH2010288, P50 CA217694, R01 CA228216
Cycle for Survival Fund	U54 CA224070, R01 CA238237
Consejo Nacional de Ciencia y Tecnología of Mexico	A1-S-30165, A3-S-31603, IA202020
H2020 Program of the European Union	955575
Cancer Biology	R01 CA103846, P01CA63222
European Research Council	756017

Keywords

animal models
drug discovery
immunotherapy
melanoma
targeted therapy
therapeutics
tumor microenvironment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ccell.2021.01.011

Cite this

Patton, E. E., Mueller, K. L., Adams, D. J., Anandasabapathy, N., Aplin, A. E., Bertolotto, C., Bosenberg, M., Ceol, C. J., Burd, C. E., Chi, P., Herlyn, M., Holmen, S. L., Karreth, F. A., Kaufman, C. K., Khan, S., Kobold, S., Leucci, E., Levy, C., Lombard, D. B., ... Merlino, G. (2021). Melanoma models for the next generation of therapies. Cancer Cell, 39(5), 610-631. https://doi.org/10.1016/j.ccell.2021.01.011

@article{c410f07de2ed49f08a8912336ecf08bf,

title = "Melanoma models for the next generation of therapies",

abstract = "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.",

keywords = "animal models, drug discovery, immunotherapy, melanoma, targeted therapy, therapeutics, tumor microenvironment",

author = "Patton, {E. Elizabeth} and Mueller, {Kristen L.} and Adams, {David J.} and Niroshana Anandasabapathy and Aplin, {Andrew E.} and Corine Bertolotto and Marcus Bosenberg and Ceol, {Craig J.} and Burd, {Christin E.} and Ping Chi and Meenhard Herlyn and Holmen, {Sheri L.} and Karreth, {Florian A.} and Kaufman, {Charles K.} and Shaheen Khan and Sebastian Kobold and Eleonora Leucci and Carmit Levy and Lombard, {David B.} and Lund, {Amanda W.} and Marie, {Kerrie L.} and Marine, {Jean Christophe} and Richard Marais and Martin McMahon and Robles-Espinoza, {Carla Daniela} and Ronai, {Ze'ev A.} and Yardena Samuels and Soengas, {Maria S.} and Jessie Villanueva and Weeraratna, {Ashani T.} and White, {Richard M.} and Iwei Yeh and Jiyue Zhu and Zon, {Leonard I.} and Hurlbert, {Marc S.} and Glenn Merlino",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = may,

day = "10",

doi = "10.1016/j.ccell.2021.01.011",

language = "אנגלית",

volume = "39",

pages = "610--631",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "5",

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Patton, EE, Mueller, KL, Adams, DJ, Anandasabapathy, N, Aplin, AE, Bertolotto, C, Bosenberg, M, Ceol, CJ, Burd, CE, Chi, P, Herlyn, M, Holmen, SL, Karreth, FA, Kaufman, CK, Khan, S, Kobold, S, Leucci, E, Levy, C, Lombard, DB, Lund, AW, Marie, KL, Marine, JC, Marais, R, McMahon, M, Robles-Espinoza, CD, Ronai, ZA, Samuels, Y, Soengas, MS, Villanueva, J, Weeraratna, AT, White, RM, Yeh, I, Zhu, J, Zon, LI, Hurlbert, MS & Merlino, G 2021, 'Melanoma models for the next generation of therapies', Cancer Cell, vol. 39, no. 5, pp. 610-631. https://doi.org/10.1016/j.ccell.2021.01.011

TY - JOUR

T1 - Melanoma models for the next generation of therapies

AU - Patton, E. Elizabeth

AU - Mueller, Kristen L.

AU - Adams, David J.

AU - Anandasabapathy, Niroshana

AU - Aplin, Andrew E.

AU - Bertolotto, Corine

AU - Bosenberg, Marcus

AU - Ceol, Craig J.

AU - Burd, Christin E.

AU - Chi, Ping

AU - Herlyn, Meenhard

AU - Holmen, Sheri L.

AU - Karreth, Florian A.

AU - Kaufman, Charles K.

AU - Khan, Shaheen

AU - Kobold, Sebastian

AU - Leucci, Eleonora

AU - Levy, Carmit

AU - Lombard, David B.

AU - Lund, Amanda W.

AU - Marie, Kerrie L.

AU - Marine, Jean Christophe

AU - Marais, Richard

AU - McMahon, Martin

AU - Robles-Espinoza, Carla Daniela

AU - Ronai, Ze'ev A.

AU - Samuels, Yardena

AU - Soengas, Maria S.

AU - Villanueva, Jessie

AU - Weeraratna, Ashani T.

AU - White, Richard M.

AU - Yeh, Iwei

AU - Zhu, Jiyue

AU - Zon, Leonard I.

AU - Hurlbert, Marc S.

AU - Merlino, Glenn

PY - 2021/5/10

Y1 - 2021/5/10

N2 - 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.

AB - 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.

KW - animal models

KW - drug discovery

KW - immunotherapy

KW - melanoma

KW - targeted therapy

KW - therapeutics

KW - tumor microenvironment

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U2 - 10.1016/j.ccell.2021.01.011

DO - 10.1016/j.ccell.2021.01.011

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C2 - 33545064

AN - SCOPUS:85100410854

SN - 1535-6108

VL - 39

SP - 610

EP - 631

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

Melanoma models for the next generation of therapies

Abstract

Funding

Keywords

UN SDGs

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