ArticleCell reports. Medicine2024
EGFR-directed antibodies promote HER2 ADC internalization and efficacy.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed.
- Perspectives of EGFR co-targeting with nanocarriers for anti-TNBC purposes.Genes & diseases · 2026Review
- AKAP13 regulates GLI1/ULK1 axis and drive tumor resistance to next-generation HER2-targeted therapies.Oncogene · 2026Article
- Protocol for designing and evaluating antibody-drug conjugates to promote endocytosis and lysosomal trafficking.STAR protocols · 2026Article
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- Article
- Review
- The next generation of antibody-drug conjugates.Nature medicine · 2026Review
- Precision Therapeutics in Pancreatic Cancer: Emerging Targeted, Immune, and Antibody-Drug Conjugate Strategies Exemplified by Adagrasib, Dostarlimab, and Trastuzumab Deruxtecan.Journal of clinical medicine · 2026Review
- NAV-005, a high-affinity MUC16/CA125 antagonist for the treatment of humoral immunosuppressed cancers.BMC cancer · 2026Article
- Antibody-drug conjugates in breast cancer: Progress and future directions.Cell reports. Medicine · 2026Review
- Pertuzumab Enhances the Antitumor Activity of T-DXd in HER2-Positive Gastric Cancer Cells.Molecular cancer therapeutics · 2026Article
- Stress-responsive membrane proteins as execution nodes of tumor cell adaptation to microenvironmental stress.Oncogene · 2026Review
- Epidermal Growth Factor Receptor/KIT-Linked Proliferative Bias in Normal Breast Lobules from Matched Non-Hispanic Black and White Women Is Rapidly Reversible by Receptor Tyrosine Kinase Inhibition.The American journal of pathology · 2026Article
- Izalontamab Brengitecan in Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations Outside of ClassicalJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Article
- Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates in Oncology.Pharmaceutics · 2026Review
- Combining an anti-HER2 antibody-drug conjugate with an anti-nectin-4 antibody-drug conjugate enhances efficacy in breast cancer and gastric cancer models.Cancer cell international · 2026Article
- Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Bio-Polymers Based Functionalized Hydrogel Carriers for Targeted Oncology Therapies: Current Progress and Future Perspectives.International journal of nanomedicine · 2026Review
- Bispecific antibody-drug conjugates: a modular blueprint for next-generation cancer therapeutics.Archives of pharmacal research · 2026Review
- Determinants of sensitivity to HER2-targeted antibody drug conjugates in urothelial cancer.Nature communications · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
Abstract
Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor receptor 2 (HER2)-targeting antibody drug conjugate that has remarkable activity in HER2-positive cancers. However, the degree of benefit of T-DXd is not uniform among solid tumors even with high levels of HER2. Despite high HER2 expression, the HER2/T-DXd complex may not always undergo internalization and payload release dependent on the receptor's conformation and context. We hypothesize that epidermal growth factor receptor (EGFR), a dimerization partner of HER2, can modulate HER2 trafficking through endocytic pathways and affect T-DXd uptake. We demonstrate that elevated EGFR expression levels can promote EGFR/HER2 heterodimer formation and suppress T-DXd internalization and efficacy. Knockdown of EGFR expression or pharmacologic stimulation of EGFR endocytosis with EGFR monoclonal antibodies restores T-DXd trafficking and antitumor activity in EGFR-overexpressing cancers in vivo. Our results reveal EGFR overexpression to be a potential mechanism of resistance to T-DXd, which can be overcome by combination therapy strategies targeting EGFR.
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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.