Mark D. Pegram
马克·佩格拉姆
MD
Susy Yuan-Huey Hung Professor, Division of Oncology; Co-Director, Breast Oncology Program, Stanford Cancer Institute斯坦福大学肿瘤学系苏茜·袁慧·洪教授；斯坦福癌症研究所乳腺肿瘤项目联合主任
👥Biography 个人简介
Mark D. Pegram, MD is the Susy Yuan-Huey Hung Professor in the Division of Oncology and Co-Director of the Breast Oncology Program at Stanford Cancer Institute. He is one of the pioneering scientists in HER2-targeted therapy and was among the original investigators in the first-in-human clinical trials of trastuzumab in the late 1980s and early 1990s at UCLA. Dr. Pegram's early mechanistic work demonstrated that trastuzumab exerts anti-tumor effects through multiple mechanisms including ADCC and downstream HER2 signaling suppression, and established the rationale for combining trastuzumab with chemotherapy. More recently, he has focused on the biology and clinical development of novel HER2-targeted agents including bispecific antibodies (such as zanidatamab targeting HER2/ECD domains) and small molecule tyrosine kinase inhibitors. He contributed to translational and biomarker studies supporting the HER2CLIMB trial of tucatinib plus trastuzumab and capecitabine, which demonstrated significant OS benefit including in patients with active brain metastases and led to FDA approval. Dr. Pegram directs an active laboratory investigating HER2 pathway biology, resistance to anti-HER2 therapy, and novel combination immunotherapy approaches in HER2+ breast cancer. He has published more than 300 peer-reviewed articles and holds multiple patents in cancer therapeutics.
🧪Research Fields 研究领域
🎓Key Contributions 主要贡献
Early Clinical Development of Trastuzumab in HER2+ Breast Cancer
Was among the first clinical investigators in phase I/II trials of trastuzumab at UCLA in the early 1990s, generating foundational clinical evidence for anti-HER2 therapy efficacy and safety, establishing the pharmacodynamic rationale for trastuzumab plus chemotherapy combinations that transformed HER2+ breast cancer treatment.
Mechanisms of HER2 Antibody Action and ADCC
Conducted seminal laboratory investigations into the mechanisms of action of trastuzumab and pertuzumab, characterizing the roles of antibody-dependent cellular cytotoxicity (ADCC), PI3K/AKT signaling suppression, and HER2 receptor shedding in determining therapeutic response and resistance in HER2-overexpressing tumors.
Tucatinib and HER2CLIMB — TKI Strategy in HER2+ Breast Cancer with Brain Metastases
Contributed translational and biomarker research supporting the HER2CLIMB trial, which demonstrated that tucatinib (a highly selective HER2 TKI) combined with trastuzumab and capecitabine significantly improved PFS and OS, with particular benefit in patients with active HER2+ brain metastases—an underserved population historically excluded from trials.
HER2 Bispecific Antibody Development
Leads investigations into next-generation bispecific antibodies targeting dual HER2 epitopes such as zanidatamab, characterizing their mechanistic superiority over single-domain HER2 antibodies through enhanced receptor internalization, clustering, and NK cell-mediated ADCC, supporting their evaluation in phase II/III trials in biliary tract and breast cancers.
Representative Works 代表性著作
Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer (HER2CLIMB)
New England Journal of Medicine (2020)
HER2CLIMB phase II trial demonstrating that adding tucatinib to trastuzumab and capecitabine significantly improved PFS and OS including in patients with active HER2+ brain metastases, leading to FDA approval in 2020.
Phase II study of trastuzumab plus cisplatin in HER2/neu-overexpressing metastatic breast cancer
Journal of Clinical Oncology (1998)
Early landmark trial demonstrating clinical activity of trastuzumab plus cisplatin in HER2-overexpressing metastatic breast cancer, establishing the feasibility of combining anti-HER2 antibody therapy with platinum-based chemotherapy.
HER2/neu as a predictive marker of response to breast cancer therapy
Breast Cancer Research and Treatment (1998)
Foundational review establishing HER2 overexpression as a predictive biomarker for anthracycline benefit and trastuzumab response, shaping early precision oncology frameworks for HER2+ breast cancer.
Zanidatamab, a novel bispecific antibody targeting HER2: Preclinical characterization and clinical development
Cancer Research (2021)
Preclinical and translational characterization of zanidatamab, demonstrating enhanced anti-HER2 activity through biepitopic HER2 binding and ADCC, supporting phase II trials in HER2-amplified biliary tract cancer and breast cancer.
🏆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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