ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021
An Elaborate New Linker System Significantly Enhances the Efficacy of an HER2-Antibody-Drug Conjugate against Refractory HER2-Positive Cancers.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 31 citations in OpenAlex.
- Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a detailed safety analysis of the randomized OptiTROP-Breast01 study.Breast cancer research : BCR · 2026Trial
- Antibody-Drug Conjugates Reshape the Landscape of Cancer Therapy: Evolution, Challenges and Future Perspectives from the Concept of "Magic Bullet" to Clinical Application.Current oncology reports · 2026Review
- Clinicopathological features and prognosis of HER2-low gastric cancer: a real-world retrospective cohort study.World journal of surgical oncology · 2026Article
- Site-specific ligase-dependent conjugation with ring-opening linker improves safety and stability of HER2-targeting ADCs.Nature communications · 2025Article
- The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform.Journal of pharmaceutical analysis · 2025Review
- Antibody-Drug Conjugates in Breast Cancer: Navigating Innovations, Overcoming Resistance, and Shaping Future Therapies.Biomedicines · 2025Review
- New targets and strategies in treatment of metastatic gastric cancer.Future oncology (London, England) · 2025Review
- Evolution of HER2-low expression from primary to paired metastatic gastric cancer lesions.NPJ precision oncology · 2025Article
- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- Evolving Landscape of HER2-Targeted Therapies for Gastric Cancer Patients.Current treatment options in oncology · 2025Review
- Small-Molecule Mitotic Inhibitors as Anticancer Agents: Discovery, Classification, Mechanisms of Action, and Clinical Trials.International journal of molecular sciences · 2025Review
- Antibody-drug conjugates in breast cancer treatment: resistance mechanisms and the role of therapeutic sequencing.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Review
- Review
- Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Review
- HER2-targeting antibody drug conjugate FS-1502 in HER2-expressing metastatic breast cancer: a phase 1a/1b trial.Nature communications · 2024Article
- Xenograft and organoid models in developing precision medicine for gastric cancer (Review).International journal of oncology · 2024Review
- ADCdb: the database of antibody-drug conjugates.Nucleic acids research · 2024Article
- Introduction of Carbonyl Groups into Antibodies.Molecules (Basel, Switzerland) · 2023Review
- Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening.Cell death discovery · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast and gastric cancers and this causes poor clinical outcomes. Although both T-DM1 and Enhertu are approved as an HER2-targeting antibody-drug conjugate (ADC), the effects of these drugs are still not satisfactory to eradicate diverse tumors expressing HER2. To address this shortfall in HER2-targeted therapeutics, an elaborate cleavable linker is created and a novel HER2-targeting ADC composed with trastuzumab and monomethyl auristatin F, which is being investigated in a phase 1 clinical trial and is referred to as LegoChem Bisciences-ADC (LCB-ADC). LCB-ADC displays a higher cytotoxic potency than T-DM1 and it also has a higher G2/M arrest ratio. In animal studies, LCB-ADC produces noticeable tumor growth inhibition compared with trastuzumab or T-DM1 in an HER2 high-expressing N87 xenograft tumor. Especially, LCB-ADC shows good efficacy in terms of suppressing tumor growth in a patient-derived xenograft (PDX) model of HER2-positive gastric cancer as well as in T-DM1-resistant models such as HER2 low-expressing HER2 low expressing JIMT-1 xenograft tumor and PDX. Collectively, the results demonstrate that LCB-ADC with the elaborate linker has a higher efficacy and greater biostability than its ADC counterparts and may successfully treat cancers that are nonresponsive to previous therapeutics.
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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.