ArticleCancer research2013
Combination of antibody that inhibits ligand-independent HER3 dimerization and a p110α inhibitor potently blocks PI3K signaling and growth of HER2+ breast cancers.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 87 citations in OpenAlex.
- Discovering anticancer drug target combinations via network-informed signaling-based approach.Communications medicine · 2025Article
- Dual membrane receptor degradation via folate receptor targeting chimera.Nature communications · 2025Article
- Targeting Signaling Excitability in Cervical and Pancreatic Cancer Cells Through Combined Inhibition of FAK and PI3K.International journal of molecular sciences · 2025Article
- DB-1310, a HER3-targeting antibody-drug conjugate, has synergistic anti-tumor activity with trastuzumab in HER2- and HER3-expressing breast cancer.Cancer biology & medicine · 2025Article
- Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma.Oncology reports · 2025Article
- Anticancer Target Combinations: Network-Informed Signaling-Based Approach to Discovery.bioRxiv : the preprint server for biology · 2024Article
- HER3 receptor and its role in the therapeutic management of metastatic breast cancer.Journal of translational medicine · 2024Review
- Role of human epidermal growth factor receptor 3 in treatment resistance of anaplastic lymphoma kinase translocated non-small cell lung cancer.Cancer biology & therapy · 2023Article
- The effects of ARID1A mutation in gastric cancer and its significance for treatment.Cancer cell international · 2023Review
- HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022Review
- Review
- A Novel miRNA Located in theBioMed research international · 2022Article
- A Phase I Study of Alpelisib in Combination with Trastuzumab and LJM716 in Patients withClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Proteomic Resistance Biomarkers for PI3K Inhibitor in Triple Negative Breast Cancer Patient-Derived Xenograft Models.Cancers · 2020Article
- Rewiring ERBB3 and ERK signaling confers resistance to FGFR1 inhibition in gastrointestinal cancer harbored an ERBB3-E928G mutation.Protein & cell · 2020Article
- HER3 targeting potentiates growth suppressive effects of the PI3K inhibitor BYL719 in pre-clinical models of head and neck squamous cell carcinoma.Scientific reports · 2019Article
- Challenges for the Clinical Development of PI3K Inhibitors: Strategies to Improve Their Impact in Solid Tumors.Cancer discovery · 2019Review
- Therapeutic Potency of PI3K Pharmacological Inhibitors of Gastrointestinal Cancer.Middle East journal of digestive diseases · 2019Review
- ErbB3 Targeting Enhances the Effects of MEK Inhibitor in Wild-Type BRAF/NRAS Melanoma.Cancer research · 2018Article
- HER3-Mediated Resistance to Hsp90 Inhibition Detected in Breast Cancer Xenografts by Affibody-Based PET Imaging.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
We examined the effects of LJM716, an HER3 (ERBB3) neutralizing antibody that inhibits ligand-induced and ligand-independent HER3 dimerization, as a single agent and in combination with BYL719, an ATP competitive p110α-specific inhibitor, against HER2-overexpressing breast and gastric cancers. Treatment with LJM716 reduced HER2-HER3 and HER3-p85 dimers, P-HER3 and P-AKT, both in vitro and in vivo. Treatment with LJM716 alone markedly reduced growth of BT474 xenografts. The combination of LJM716/lapatinib/trastuzumab significantly improved survival of mice with BT474 xenografts compared with lapatinib/trastuzumab (P = 0.0012). LJM716 and BYL719 synergistically inhibited growth in a panel of HER2+ and PIK3CA mutant cell lines. The combination also inhibited P-AKT in HER2-overexpressing breast cancer cells and growth of HER2+ NCI-N87 gastric cancer xenografts more potently than LJM716 or BYL719 alone. Trastuzumab-resistant HER2+/PIK3CA mutant MDA453 xenografts regressed completely after 3 weeks of therapy with LJM716 and BYL719, whereas either single agent inhibited growth only partially. Finally, mice with BT474 xenografts treated with trastuzumab/LJM716, trastuzumab/BYL719, LJM716/BYL719, or trastuzumab/LJM716/BYL719 exhibited similar rates of tumor regression after 3 weeks of treatment. Thirty weeks after treatment discontinuation, 14% of mice were treated with trastuzumab/LJM716/BYL719, whereas >80% in all other treatment groups were sacrificed due to a recurrent large tumor burden (P = 0.0066). These data suggest that dual blockade of the HER2 signaling network with an HER3 antibody that inhibits HER2-HER3 dimers in combination with a p110α-specific inhibitor in the absence of a direct HER2 antagonist is an effective treatment approach against HER2-overexpressing cancers.
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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.