Tanguy Y. Seiwert
唐居·塞沃特
MD
Professor of Oncology; Director, Head and Neck Cancer Program, Johns Hopkins肿瘤学教授，约翰斯·霍普金斯头颈部癌症项目主任
👥Biography 个人简介
Tanguy Y. Seiwert, MD is Professor of Oncology and Director of the Head and Neck Cancer Program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. He is recognized for leading KEYNOTE-012, the pivotal phase Ib trial that provided the first evidence of pembrolizumab activity in recurrent/metastatic HNSCC, pioneering the use of PD-1 checkpoint blockade in this disease and enabling subsequent pivotal phase III trials. Dr. Seiwert is a leader in translational genomics of HNSCC, having conducted landmark studies examining the HNSCC mutational landscape, including identification of frequently mutated driver genes (TP53, NOTCH1, CDKN2A, FAT1, CASP8) and characterization of the genomic differences between HPV-positive and HPV-negative tumors. He has advanced liquid biopsy approaches in HNSCC, using circulating tumor DNA (ctDNA) for disease monitoring, residual disease detection after treatment, and early recurrence identification. Dr. Seiwert has also worked on understanding mechanisms of intrinsic and acquired resistance to immunotherapy in HNSCC and identifying novel predictive biomarkers beyond PD-L1.
🧪Research Fields 研究领域
🎓Key Contributions 主要贡献
KEYNOTE-012 — First Clinical Evidence of Pembrolizumab Activity in HNSCC
Led the HNSCC cohort of KEYNOTE-012, a phase Ib trial that was the first to demonstrate anti-tumor activity of pembrolizumab in recurrent/metastatic HNSCC, with an overall response rate of ~18% and a manageable safety profile, directly enabling the pivotal KEYNOTE-040 and KEYNOTE-048 phase III trials.
Comprehensive Genomic Characterization of HNSCC
Contributed to landmark genomic studies including the TCGA HNSCC analysis, characterizing the mutational landscape, copy number alterations, and genomic distinctions between HPV-positive and HPV-negative tumors, and identifying recurrently mutated genes as potential therapeutic targets.
Liquid Biopsy and ctDNA in HNSCC
Developed and validated circulating tumor DNA (ctDNA) assays for HNSCC, demonstrating that ctDNA dynamics correlate with treatment response and that detectable ctDNA after definitive therapy identifies patients at high risk for recurrence who may benefit from intensified surveillance or salvage intervention.
Immunotherapy Resistance Mechanisms in HNSCC
Investigated mechanisms of primary and acquired resistance to PD-1 blockade in HNSCC, identifying alterations in interferon signaling (JAK1/2, B2M), antigen presentation, and STK11/KEAP1 pathways as potential resistance drivers, informing the design of combination strategies to overcome immune checkpoint resistance.
Representative Works 代表性著作
Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results from the Phase Ib KEYNOTE-012 Expansion Cohort
Journal of Clinical Oncology (2016)
KEYNOTE-012 HNSCC expansion cohort reporting pembrolizumab activity with ORR 18% and 12-month OS 38%, providing proof-of-concept for PD-1 inhibition in this disease.
Comprehensive Genomic Analysis Identifies SOX2 as a Frequently Amplified Gene in Small-Cell Lung Cancer
Nature Genetics (2012)
Genomic analysis identifying key driver amplifications in squamous carcinoma subtypes applicable to HNSCC characterization.
ctDNA for HNSCC response monitoring and residual disease detection
Annals of Oncology (2021)
Clinical validation of ctDNA monitoring in HNSCC demonstrating correlation of ctDNA clearance with response and association of ctDNA persistence with recurrence risk.
Comprehensive genomic characterization of head and neck squamous cell carcinomas
Nature (2015)
TCGA landmark study providing integrated genomic analysis of 279 HNSCC tumors, characterizing mutational landscape, subtypes, and therapeutic targets.
🏆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
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