Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities

Alcida Karz^#^{1

2}, Maya Dimitrova^#^{2

3}, Kevin Kleffman^{1

2}, Christopher Alvarez-Breckenridge⁴, Michael B Atkins⁵, Adrienne Boire⁶, Marcus Bosenberg⁷, Priscilla Brastianos⁸, Daniel P Cahill⁹, Qing Chen¹⁰, Sherise Ferguson⁴, Peter Forsyth¹¹, Isabella C Glitza Oliva¹², Sarah B Goldberg¹³, Sheri L Holmen¹⁴, Jonathan P S Knisely¹⁵, Glenn Merlino⁷, Don X Nguyen¹⁶, Michael E Pacold¹⁷, Eva Perez-Guijarro⁷, Keiran S M Smalley¹⁸, Hussein A Tawbi¹², Patrick Y Wen¹⁹, Michael A Davies¹², Harriet M Kluger¹³, Janice M Mehnert^{2

3}, Eva Hernando^{1

2}

Affiliations

¹ Department of Pathology, NYU Grossman School of Medicine, New York, USA.
² Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, USA.
³ Department of Medicine, NYU Grossman School of Medicine, New York, USA.
⁴ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁵ Georgetown-Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, District of Columbia, USA.
⁶ Human Oncology and Pathogenesis Program, Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, USA.
⁷ Laboratory of Cancer Biology and Genetics, Center for Cancer Research NCI, NIH, USA.
⁸ MGH Cancer Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
¹¹ Department of Neuro-Oncology and Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
¹² Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹³ Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, Connecticut, USA.
¹⁴ Huntsman Cancer Institute and Department of Surgery, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
¹⁵ Meyer Cancer Center and Department of Radiation Oncology, Weill Cornell Medicine, New York, New York, USA.
¹⁶ Department of Pathology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA.
¹⁷ Department of Radiation Oncology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.
¹⁸ Department of Tumor Biology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
¹⁹ Center for Neuro-Oncology, Dana-Farber Cancer Institute, United States, Boston, Massachusetts, USA.

^# Contributed equally.

PMID: 35912544
PMCID: PMC10171356
DOI: 10.1111/pcmr.13059

Review

Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities

Alcida Karz et al. Pigment Cell Melanoma Res. 2022 Nov.

. 2022 Nov;35(6):554-572.

doi: 10.1111/pcmr.13059. Epub 2022 Sep 1.

Authors

Affiliations

¹ Department of Pathology, NYU Grossman School of Medicine, New York, USA.
² Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, USA.
³ Department of Medicine, NYU Grossman School of Medicine, New York, USA.
⁴ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁵ Georgetown-Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, District of Columbia, USA.
⁶ Human Oncology and Pathogenesis Program, Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, USA.
⁷ Laboratory of Cancer Biology and Genetics, Center for Cancer Research NCI, NIH, USA.
⁸ MGH Cancer Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
¹¹ Department of Neuro-Oncology and Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
¹² Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹³ Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, Connecticut, USA.
¹⁴ Huntsman Cancer Institute and Department of Surgery, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
¹⁵ Meyer Cancer Center and Department of Radiation Oncology, Weill Cornell Medicine, New York, New York, USA.
¹⁶ Department of Pathology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA.
¹⁷ Department of Radiation Oncology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.
¹⁸ Department of Tumor Biology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
¹⁹ Center for Neuro-Oncology, Dana-Farber Cancer Institute, United States, Boston, Massachusetts, USA.

^# Contributed equally.

PMID: 35912544
PMCID: PMC10171356
DOI: 10.1111/pcmr.13059

Abstract

Brain metastases are the most common brain malignancy. This review discusses the studies presented at the third annual meeting of the Melanoma Research Foundation in the context of other recent reports on the biology and treatment of melanoma brain metastases (MBM). Although symptomatic MBM patients were historically excluded from immunotherapy trials, efforts from clinicians and patient advocates have resulted in more inclusive and even dedicated clinical trials for MBM patients. The results of checkpoint inhibitor trials were discussed in conversation with current standards of care for MBM patients, including steroids, radiotherapy, and targeted therapy. Advances in the basic scientific understanding of MBM, including the role of astrocytes and metabolic adaptations to the brain microenvironment, are exposing new vulnerabilities which could be exploited for therapeutic purposes. Technical advances including single-cell omics and multiplex imaging are expanding our understanding of the MBM ecosystem and its response to therapy. This unprecedented level of spatial and temporal resolution is expected to dramatically advance the field in the coming years and render novel treatment approaches that might improve MBM patient outcomes.

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Conflict of interest statement

CONFLICT OF INTEREST

Alcida Karz: None; Maya Dimitrova: None; Kevin Kleffman: None; Christopher Alvarez-Breckenridge: None; Michael B. Atkins: Has/had an advisory role for Bristol-Myers Squibb, Merck, Novartis, Eisai, Aveo, Pfizer, Werewolf, Fathom, Pneuma, Leads, Pyxis Oncology, PACT, Elpis, X4Pharma, ValoHealth, ScholarRock, Surface, Takeda, Simcha, Roche, SAB Bio, and GSK and has served as a consultant: Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, Exelixis, Iovance, COTA, Idera, Agenus, Apexigen, Asher Bio, Neoleukin, AstraZeneca, Calithera, SeaGen, and Sanofi. He reports research support to his institution from Bristol-Myers Squibb, Merck, and Pfizer. He holds stock/stock options in Pyxis Oncology, Werewolf, and Elpis; Adrienne Boire: Inventor on US Provis. Patent App. No: 62/258,044, 63/052,139. Unpaid member of SAB Evren Scientific; Marcus Bosenberg: AstraZeneca for unrelated activities; Priscilla Brastianos: Consulted for Angiochem, Genentech/Roche, Lilly, Tesaro, ElevateBio, Pfizer (Array), Dantari, SK Life Sciences, Advise Connect Inspire (ACI), Voyager Therapeutics and Sintetica, and has received grant/research support to MGH from Merck, Bristol Myers Squibb, Mirati Therapeutics, and Lilly and honoraria from Merck, Genentech/Roche, Pfizer, and Lilly; Daniel Cahill: Consulted for the Massachusetts Institute of Technology, Advise Connect Inspire, Lilly, GlaxoSmithKline, Boston Pharmaceuticals and serves on the advisory board of Pyramid Biosciences, which includes an equity interest. Honoraria and travel reimbursement from Merck for invited lectures, and from the US NIH and DOD for clinical trial and grant review; Qing Chen: None; Sherise Ferguson; Peter Forsyth: AbbVie; Biocept; Boehringer-Ingelheim; Bristol-Myers Squibb; Novocure; Isabella C. Glitza Oliva: None; Sarah Goldberg: Research funding from AstraZeneca, Boehringer Ingelheim, and Mirati. Consulting/advisory board member for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Amgen, Blueprint Medicine, Sanofi Genzyme, Daiichi-Sankyo, Regeneron, Takeda, and Janssen; Sheri Holmen: None; Jonathan Knisely: None; Glenn Merlino: None; Don X. Nguyen: Has received research funding from AstraZeneca Inc which is unrelated to the work herein; Michael E. Pacold: Holds options and has consulted for Raze Therapeutics. Consultant for aMoon Venture Fund. Consultant and research funds from Novocure. Travel funds from Thermo Fisher Scientific; Eva Perez-Guijarro: None; Keiran Smalley: None; Hussein A. Tawbi: Is a paid consultant for BMS, Merck, Novartis, Genentech, Iovance, Eisai, Pfizer, Karyopharm, Boxer Capital, and receives research funding to institution from BMS, Merck, Novartis, Genentech, GSK, Eisai, Dragongly Therapeutics, RAPT Therapeutics; Patrick Wen: Advisory Board: Agios, Astra Zeneca, Bayer, Black Diamond, Boehringer Ingelheim, Boston Pharmaceuticals, Celularity, Chimerix, Day One Bio, Genenta, Glaxo Smith Kline, Karyopharm, Merck, Mundipharma, Novartis, Novocure, Nuvation Bio, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics, VBI Vaccines; Research Support: Astra Zeneca/Medimmune, Beigene, Celgene, Chimerix, Eli Lily, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Servier, Vascular Biogenics, VBI Vaccines; Michael A. Davies: Consultant to Roche/Genentech, Array, Pfizer, Novartis, BMS, GSK, Sanofi-Aventis, Vaccinex, Apexigen, Eisai, Iovance, and ABM Therapeutics, and he has been the PI of research grants to MD Anderson by Roche/Genentech, GSK, Sanofi-Aventis, Merck, Myriad, Oncothyreon, and ABM Therapeutics; Harriet M. Kluger: Has received institutional research grants from Merck, Bristol-Myers Squibb, Apexigen. Has received personal fees from Iovance, Immunocore, Celldex, Array Biopharma, Merck, Elevate Bio, Instil Bio, Bristol-Myers Squibb, Clinigen, Shionogi, Chemocentryx, Calithera, Signatero, Giaggen, GI Reviewers; Janice M. Mehnert: Advisory board: BMS, Seagen, Novartis, Eisai, Regeneron; Consulting: Merck; Research Support: BMS, Seagen, Regeneron, Novartis, Incyte, Merck; Eva Hernando: None. The Melanoma Research Foundation thanks BMS, Novartis, Natera, and Istari Oncology for providing financial support for the Brain Metastasis Summit.

Figures

**FIGURE 1**
A summary of established molecular players in the interactions between melanoma brain metastasis cells and the cells of the brain microenvironment. Inspired by a similar figure in Srinivasan et al. 2021 and made with Biorender.com

See this image and copyright information in PMC

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Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities

Affiliations

Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical