Spatial determinants of antibody-drug conjugate SHR-A1811 efficacy in neoadjuvant treatment for HER2-positive breast cancer

IF 48.8 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2025-04-10 DOI:10.1016/j.ccell.2025.03.017

Ding Ma, Lei-Jie Dai, Xiang-Rong Wu, Cheng-Lin Liu, Shen Zhao, Hang Zhang, Li Chen, Yi Xiao, Ming Li, Yi-Zhi Zhao, Lin Yang, Tong Zhou, Jun-Jie Li, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao

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引用次数: 0

Abstract

Selecting optimal candidates for next-generation anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) remains challenging. We conduct a prespecified translational study to identify treatment biomarkers in SHR-A1811-treated HER2-positive breast cancer patients from the phase 2 neoadjuvant FASCINATE-N trial using DNA and RNA sequencing, computational pathology, and single-cell in situ spatial imaging. In the hormone receptor (HR)-negative subgroup, a higher proportion and more infiltration of immune cells (i.e., tumor-infiltrating lymphocytes [TILs]), particularly cytotoxic T cells, are associated with better treatment responses. In the HR-positive subgroup, the closeness and aggregation of HER2-strong-positive tumor cells, as opposed to a uniform distribution, are linked to a lower response rate and HER2 luminal-like (HER2-LUM) subtype, which more closely resembles HR+/HER2− breast cancer. In addition, we develop a clinically practical predictive model capable of predicting neoadjuvant treatment responses to SHR-A1811 and other novel ADCs based on clinicopathological characteristics and pathological images.

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.