Evidence map›Paper›PMID 42594874›Full record

ArticleCell reports. Medicine2026

Spatial proteogenomic profiling uncovers sensitization strategies for antibody-drug conjugate in HER2-positive breast cancer.

Yu-Wen Cai, Shu-Han Jia, Hao Wang, Hong Hu, Yan-Wu Zhang, Zhi-Ming Shao, Han-Dong Sun, Ke-Da Yu

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PubMed Full text at PMC Publisher
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Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

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No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Yu-Wen CaiDepartment of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Shu-Han JiaDepartment of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Hao WangDepartment of Breast, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610044, China.
Hong HuDivision of Breast Surgery, Department of General Surgery, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China.
Yan-Wu ZhangDepartment of Breast Surgery, the Third Affiliated Hospital of Zhengzhou University, No. 7 Kangfuqian Street, Erqi District, Zhengzhou 450052, China.
Zhi-Ming ShaoDepartment of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Han-Dong SunDepartment of Breast, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing 210004, China. Electronic address: sunhandong@njmu.edu.cn.
Ke-Da YuDepartment of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China. Electronic address: yukeda@fudan.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) have transformed the treatment of HER2-positive breast cancer, yet resistance remains poorly understood. Using imaging mass cytometry, we profiled 157 regions of interest comprising 912,360 single cells from 47 HER2-positive/hormone receptor-negative breast cancers treated with SHR-A1811 in the FASCINATE-N trial. Spatial proteomic analyses identified two determinants of ADC response: elevated tumor-cell H3K27ac expression was associated with improved ADC efficacy, whereas collagen-positive fibroblasts mediated resistance. Combining ADC with the histone deacetylase inhibitor chidamide or the collagen-modulating agent losartan produced synergistic antitumor effects in preclinical models. These biomarkers and therapeutic vulnerabilities were independently validated in patients with advanced HER2-positive disease receiving trastuzumab deruxtecan. Moreover, based on these spatial features, we developed a clinically applicable ADC barrier prediction model that can be implemented using multiplex immunofluorescence. Taken together, our findings reveal actionable spatial determinants of ADC efficacy and suggest potential combination therapeutic strategies.

Indexed as

Breast NeoplasmsErb-b2 Receptor Tyrosine KinasesImmunoconjugatesProteogenomicsAnimalsCell Line, TumorFemaleHumansTrastuzumabERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesImmunoconjugatesTrastuzumabantibody-drug conjugatebreast cancerimaging mass cytometryspatial proteogenomic profiling

Identifiers

PMID42594874
PMCPMC13589474

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.