ArticleNPJ breast cancer2025
Mechanisms of resistance to trastuzumab deruxtecan in breast cancer elucidated by multi-omic molecular profiling.
Article in NPJ breast cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- A modular framework for antibody-drug conjugate biomarkers.Nature reviews. Clinical oncology · 2026Review
- Right-sizing treatment for HER2-positive breast cancer: evolving algorithms across the disease continuum.Nature reviews. Clinical oncology · 2026Review
- Antibody-drug conjugates in breast cancer: redefining targeted therapy.The Journal of clinical investigation · 2026Review
- Review
- The next generation of antibody-drug conjugates.Nature medicine · 2026Review
- Targeting TROP2 and Exploiting AUNIP as a Determinant of ADC Cytotoxicity and Chemosensitivity in HNSCC and ESCA Cancers.Molecular carcinogenesis · 2026Article
- Real-world clinical outcomes of Trastuzumab Deruxtecan in HER2-expressing ovarian and endometrial Cancer.Gynecologic oncology reports · 2026Article
- From Unmet Medical Need to Drug Candidate: A Translational Therapeutic Development Roadmap Illustrated by Dual-Payload Antibody-Drug Conjugates.Biomolecules · 2026Review
- Dynamic monitoring of antibody drug conjugates targeting TROP2 or HER2 in breast cancer using circulating tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Real-World Effectiveness and Safety of Tucatinib, Trastuzumab, and Capecitabine in HER2-Positive Advanced Breast Cancer: A Multicenter Portuguese Study.European journal of breast health · 2026Article
- Statins enhance trastuzumab deruxtecan efficacy: preclinical synergy in HER2-negative models and clinical benefit in HER2-positive metastatic breast cancer.Experimental hematology & oncology · 2026Article
- Antibody-drug conjugates in breast cancer: Progress and future directions.Cell reports. Medicine · 2026Review
- Review
- Payload Diversification Overcomes Resistance and Guides Sequential Antibody-Drug Conjugate Therapy in Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Metastatic Triple Negative Breast Cancer: Navigating a Rapidly Evolving Therapeutic Landscape.Oncology research · 2026Review
- Antibody-drug conjugates and beyond in platinum-resistant ovarian cancer: A comprehensive review of emergent strategies.Therapeutic advances in medical oncology · 2026Review
- Decoding Breast Cancer: Emerging Molecular Biomarkers and Novel Therapeutic Targets for Precision Medicine.International journal of molecular sciences · 2025Review
- Trastuzumab deruxtecan in the treatment of HER2-positive gastric cancer: a comprehensive review.Future oncology (London, England) · 2025Review
- Antibody-drug conjugates in breast cancer: mechanisms of resistance and future therapeutic perspectives.NPJ breast cancer · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate successfully used to treat HER2-low and HER2-positive metastatic breast cancer, but resistance consistently develops. Using multivariate Cox proportional hazards in a real-world cohort of 2,799 patients with breast cancer, we aimed to identify clinically relevant T-DXd resistance mechanisms. In patients with samples collected prior to T-DXd treatment, higher expression of ERBB2 (HER2) and lower expression of ABCC1 (an ATP-binding cassette transporter involved in drug efflux) were significantly associated with longer T-DXd-related overall survival (OS); ABCC1 predicted OS independently of HER2. Furthermore, mutations in several genes were enriched in post-T-DXd samples compared to unmatched T-DXd-naïve samples, including ERBB2, NFE2L2 (a transcriptional activator of ABCC1), and KEAP1 (a negative regulator of NFE2L2), indicating plausible resistance mechanisms related to HER2 target levels and ABCC1-mediated drug efflux. Identifying such resistance mechanisms might lead to improved methods of precision oncology and novel therapeutic approaches to overcome resistance.
Identifiers
What OpenQuestion holds
Registered trials
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.