Ryan J. Sullivan
瑞安·沙利文
MD
Associate Professor of Medicine; Director, Melanoma Program; Associate Director, Cancer Clinical Discovery医学副教授，黑色素瘤项目主任
👥Biography 个人简介
Ryan J. Sullivan, MD is Associate Professor of Medicine at Harvard Medical School, Director of the Melanoma Program at Massachusetts General Hospital, and Associate Director of Cancer Clinical Discovery. He is a highly productive translational clinical researcher specializing in the mechanisms of adaptive resistance to BRAF/MEK-targeted therapy and to immune checkpoint inhibitors in melanoma, with a particular focus on the unique biology and therapeutic challenges of uveal melanoma—the most common intraocular malignancy in adults, for which no approved targeted therapies existed until recently. Dr. Sullivan co-led the pivotal IMCgp100-202 (KIMMTRAK) trial, which demonstrated that the bispecific T-cell engager tebentafusp (targeting gp100 peptide-HLA) improved overall survival versus investigator's choice in HLA-A*02:01-positive metastatic uveal melanoma—marking the first survival benefit demonstrated in this disease and the first approved therapy for uveal melanoma. He also leads extensive translational programs examining tumor immune editing, MHC loss, and IFN-γ pathway alterations as mechanisms of adaptive immune resistance in cutaneous melanoma.
🧪Research Fields 研究领域
🎓Key Contributions 主要贡献
IMCgp100-202: Tebentafusp — First Approved Therapy for Uveal Melanoma
Co-led the IMCgp100-202 phase III trial demonstrating that tebentafusp (a bispecific T-cell engager targeting gp100/HLA-A*02:01) significantly improved overall survival versus investigator's choice (dacarbazine, pembrolizumab, or ipilimumab) in treatment-naïve metastatic uveal melanoma—the first randomized trial to demonstrate an OS benefit in this disease—leading to FDA approval of tebentafusp in 2022 as the first approved therapy for uveal melanoma.
Adaptive Resistance to BRAF Inhibition: MAPK Reactivation and Phenotype Switching
Led extensive translational analyses of on-treatment and progression biopsies from BRAF inhibitor-treated melanoma patients, characterizing early adaptive MAPK reactivation, transcriptomic phenotype switching from proliferative to invasive melanoma cell states, and the role of non-cell-autonomous stromal signals in mediating rapid drug tolerance—providing mechanistic insights guiding combination strategies.
Mechanisms of Adaptive Immune Resistance in Melanoma
Conducted systematic profiling of pre- and post-progression tumor samples from melanoma patients treated with anti-PD-1 therapy, identifying interferon-gamma pathway loss (JAK1/2 mutations), MHC-I downregulation, and CD8+ T-cell exclusion as dominant adaptive immune resistance mechanisms, and is leading clinical trials of rational combinations to overcome each mechanism.
MGH Melanoma Program Leadership and Early-Phase Trial Development
Directs the MGH Melanoma Program, one of the most active early-phase melanoma trial sites in the United States, overseeing a portfolio of over 15 concurrent investigational protocols examining novel BRAF/MEK inhibitor combinations, anti-LAG-3/TIM-3/TIGIT agents, STING agonists, and adoptive cell therapy approaches in melanoma.
Representative Works 代表性著作
Tebentafusp versus Investigator's Choice in Metastatic Uveal Melanoma (IMCgp100-202)
New England Journal of Medicine (2021)
Phase III trial demonstrating that tebentafusp improved overall survival (1-year OS 73% vs. 59%) versus investigator's choice in HLA-A*02:01-positive metastatic uveal melanoma, leading to the first approved therapy for this disease.
Suppression of Adaptive Resistance to BRAF Inhibitor Therapy by Co-targeting of MAP3K1
Nature Communications (2022)
Identified MAP3K1 as a mediator of adaptive BRAF inhibitor resistance and demonstrated that co-targeting MAP3K1 suppresses early tolerance mechanisms, providing a rationale for novel triple-targeted combination strategies.
Melanoma Brain Metastases in the Era of Targeted BRAF and Immunotherapy
Journal of Clinical Oncology (2020)
Comprehensive analysis of intracranial response rates, survival outcomes, and treatment sequencing for BRAF-targeted therapy and immunotherapy in melanoma brain metastases, informing management guidelines.
Efficacy and Safety of Relatlimab plus Nivolumab by Line of Therapy in Advanced Melanoma
Journal for ImmunoTherapy of Cancer (2023)
Retrospective and prospective analyses characterizing relatlimab plus nivolumab efficacy across prior treatment lines and tumor subgroups in advanced melanoma, supporting broad application of this LAG-3 combination.
🏆Awards & Recognition 奖项与荣誉
📄Data Sources 数据来源
Last updated: 2026-04-06 | All information from publicly available academic sources
Related Experts 相关专家
Antoni Ribas
UCLA Jonsson Comprehensive Cancer Center
Drew M. Pardoll
Johns Hopkins University
Padmanee Sharma
MD Anderson Cancer Center
Naiyer A. Rizvi
Columbia University Irving Medical Center
关注 瑞安·沙利文 的研究动态
Follow Ryan J. Sullivan's research updates
留下邮箱，当我们发布与 Ryan J. Sullivan（Massachusetts General Hospital / Harvard Medical School）相关的新研究或访谈时，我们会通知你。
Explore More Experts
Discover the researchers shaping the future of cancer treatment