ArticleInvestigational new drugs2025
A novel anti-HER2/EGFR bispecific antibody-drug conjugate demonstrates promising antitumor efficacy and overcomes resistance to HER2- or EGFR-targeted ADCs.
Article in Investigational new drugs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed.
- Right-sizing treatment for HER2-positive breast cancer: evolving algorithms across the disease continuum.Nature reviews. Clinical oncology · 2026Review
- HER2 assessment in urothelial carcinoma: standardization challenges and the path forward.Cancer metastasis reviews · 2026Review
- Landscape of T-cell bispecific antibodies in cancer therapy: therapeutic strategies, challenges and future prospection.Molecular cancer · 2026Review
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates in Oncology.Pharmaceutics · 2026Review
- Formulation Matters: The Overlooked Engine of Stability and Success in Antibody-Drug Conjugates.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- Trastuzumab deruxtecan in the treatment of HER2-positive gastric cancer: a comprehensive review.Future oncology (London, England) · 2025Review
- Precision navigation through the labyrinth: overcoming EGFR resistance in non-Small cell lung cancer.Annals of medicine · 2025Review
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Chemotherapeutic Drug-Antibody Conjugates (ChemoBodies): Recent Advances and Future Directions.Current oncology reports · 2025Review
- Therapeutic challenges in HER2-targeted antibody therapies: trastuzumab and its ADC derivatives in breast cancer.American journal of cancer research · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2 and EGFR are frequently co-expressed in various tumors. While antibody-drug conjugates (ADCs) targeting HER2, such as T-DM1 and T-Dxd, have shown remarkable antitumor effects in clinical responses, their effectiveness is constrained by drug resistance. EGFR amplification or high expression is one of the factors that lead to resistance against HER2-targeted ADCs. Likewise, the amplification of HER2 may lead to the development of resistance to EGFR-targeted therapies. To overcome these challenges, we, therefore, developed a bispecific antibody (B2C4) that targets HER2 and EGFR. B2C4 exhibited strong binding affinity and internalization activity in tumor cells with high expression of HER2 and EGFR, as well as in those with high expression of either target. B2C4 was then conjugated with vc-MMAE to create a bispecific ADC (B2C4-MMAE) with an average DAR of 4.05. By effectively engaging both arms of the bispecific ADC, B2C4-MMAE demonstrated significant antitumor activity in tumor cells and animal models that were unresponsive HER2- or EGFR-targeted ADCs. B2C4-MMAE could serve as an alternative therapeutic option for tumors that are resistant to single-target treatments. Additionally, B2C4-MMAE exhibited potential in treating tumors resistant to T-Dxd, underscoring its promise as a treatment for challenging cases.
Indexed as
Identifiers
39982632What 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.