ArticleAsian Pacific journal of cancer prevention : APJCP2018
Differential Effects of Inhibitory and Stimulatory Anti-HER2 Monoclonal Antibodies on AKT/ERK Signaling Pathways
Article in Asian Pacific journal of cancer prevention : APJCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- The antineoplastic effects of nuciferine on hepatocellular carcinoma are associated with suppression of the HER2-AKT/ERK1/2 signaling pathway.Discover oncology · 2025Article
- Differential tumor inhibitory effects induced by HER3 extracellular subdomain-specific mouse monoclonal antibodies.Cancer chemotherapy and pharmacology · 2022Article
- Potent synergistic anti-tumor activity of a novel humanized anti-HER2 antibody hersintuzumab in combination with trastuzumab in xenograft models.Investigational new drugs · 2021Article
- A Novel Anti-HER2 Bispecific Antibody With Potent Tumor Inhibitory EffectsFrontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Homo- and heterodimerization of the receptor tyrosine kinase HER2 hyperactivate several downstream signaling pathways, leading to uncontrolled growth and proliferation of tumor cells. Anti-HER2 monoclonal antibodies (mAbs) may induce different effects on HER2 dimerization and signaling. Methods: The effect of two inhibitory (2A8, 1T0) and one stimulatory (1H9) anti-HER2 mAbs either alone or in combination with trastuzumab was investigated on AKT and ERK signaling pathways and HER2 degradation in a human breast cancer cell line (BT-474) by Western blotting. Result: While 1H9 mAb had no significant effect on AKT and ERK signaling pathways, 1T0 and 2A8 mAbs inhibited phosphorylation of both pathways. Combination of 1T0 mAb with trastuzumab resulted in significant synergistic inhibition of both pathways and HER2 degradation, much more potently than the combination of trastuzumab and pertuzumab. Conclusion: Our data indicate that anti-HER2 mAbs may induce different signaling pathways depending on their effect on tumor cell growth and proliferation. The significant inhibition of ERK and AKT phosphorylation by 1T0 alone or particularly in combination with trastuzumab suggests its potential therapeutic application for targeted immunotherapy of HER2 overexpressing malignancies.
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