ReviewBritish journal of cancer2020
Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer.
Review in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06125834 (Trastuzumab Emtansine), which is not on this map. Cited by 182 papers, 1 of them a synthesis that pooled 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.
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.
Trastuzumab Emtansine (T-DM1) Treatment in HER2-positive Breast Cancer Patients With Progressive Disease After TKIs or HP Therapy: a Multicenter, Single-arm, Phase II Study
Who cites it
182 citing papers in PubMed, 1 synthesis or guideline pooled it, 278 citations in OpenAlex.
- Economic evaluation of antibody-drug conjugates (ADCs) in patients with breast cancer: systematic review.European journal of clinical pharmacology · 2025Pooled it
- NSABP FB-10: a phase Ib/II trial evaluating ado-trastuzumab emtansine (T-DM1) with neratinib in women with metastatic HER2-positive breast cancer.Breast cancer research : BCR · 2024Trial
- Article
- A novel extracellular vesicle-engineered immunotherapy drug for Her2Journal of advanced research · 2026Article
- ICAM1-targeted costimulation extends HER2 CAR T cytotoxicity to HER2-low and HER2-negative tumors through synergy with TCR signaling.Molecular therapy. Oncology · 2026Article
- Trastuzumab treatment is associated with ferroptosis-related alterations in HER2-positive breast cancer organoids.Cancer chemotherapy and pharmacology · 2026Article
- Antibody-Drug Conjugates in Lung Cancer: Promise, Progress, and Persistent Challenges.Current issues in molecular biology · 2026Review
- The Dual Role of Human UDP-Glucuronosyltransferase-Mediated Metabolism in Tumor Drug Resistance: Mechanisms and Prospects.International journal of molecular sciences · 2026Review
- A novel CRLF2-targeted antibody-drug conjugate exhibits potent anti-leukemic activity against Ph-like acute lymphoblastic leukemia.Leukemia · 2026Article
- Duocarmycin-Bearing Antibody-Mimetic Drug Conjugate Combined With an ATR Inhibitor Results in Complete Tumor Regression in a KPL-4 Xenograft Model.Cancer medicine · 2026Article
- Antibody-drug conjugates in breast cancer brain and leptomeningeal metastases: mechanistic insights and therapeutic progress.Cancer metastasis reviews · 2026Review
- Prognostic Role of Inflammatory Indices and Real-World Outcomes in HER2-Positive Metastatic Breast Cancer Treated with Trastuzumab Emtansine.Diagnostics (Basel, Switzerland) · 2026Article
- Antibody-drug conjugate sequencing in HER2-positive metastatic breast cancer: Real-world outcomes of trastuzumab deruxtecan with and without prior T-DM1 exposure.Breast (Edinburgh, Scotland) · 2026Article
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Evolving antibody-drug conjugates in breast cancer from precision delivery to tumor microenvironment reprogramming.Journal of hematology & oncology · 2026Review
- In Vivo Studies of [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Antibody-Drug Conjugates in Oncology: Principles, Clinical Development, and Future Directions.MedComm · 2026Review
- Overcoming resistance to antibody-drug conjugates: mechanisms and emerging strategies.The oncologist · 2026Review
- Pan-cancer multi-omic ERBB2-HER2 characterization using next-generation sequencing and quantitative proteomics.NPJ precision oncology · 2026Article
- Antibody-drug conjugates in gastric cancer: clinical advances and resistance mechanisms.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Review
122 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) is approved for the treatment of metastatic, HER2-positive breast cancer after prior trastuzumab and taxane therapy, and has also demonstrated efficacy in the adjuvant setting in incomplete responders to neoadjuvant therapy. Despite its objective activity, intrinsic and acquired resistance to T-DM1 remains a major clinical challenge. T-DM1 mediates its activity in a number of ways, encompassing HER2 signalling blockade, Fc-mediated immune response and payload-mediated microtubule poisoning. Resistance mechanisms relating to each of these features have been demonstrated, and we outline the findings of these studies in this review. In our overview of the substantial literature on T-DM1 activity and resistance, we conclude that the T-DM1 resistance mechanisms most strongly supported by the experimental data relate to dysfunctional intracellular metabolism of the construct and subversion of DM1-mediated cell killing. Loss of dependence on signalling initiated by HER2-HER2 homodimers is not substantiated as a resistance mechanism by clinical or experimental studies, and the impact of EGFR expression and tumour immunological status requires further investigation. These findings are instructive with respect to strategies that might overcome T-DM1 resistance, including the use of second-generation anti-HER2 antibody-drug conjugates that deploy alternative linker-payload chemistries.
Indexed as
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.