ArticleOncotarget2016
Heregulin-expressing HER2-positive breast and gastric cancer exhibited heterogeneous susceptibility to the anti-HER2 agents lapatinib, trastuzumab and T-DM1.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Establishment of a trastuzumab-resistant extramammary Paget disease model: loss of PTEN as a potential mechanism.British journal of cancer · 2024Article
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.Acta pharmacologica Sinica · 2024Article
- HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments.Cancers · 2024Review
- Heregulin-induced cell migration is prevented by trastuzumab and trastuzumab-emtansine in HER2+ breast cancer.Breast cancer research and treatment · 2021Article
- HER2-/HER3-Targeting Antibody-Drug Conjugates for Treating Lung and Colorectal Cancers Resistant to EGFR Inhibitors.Cancers · 2021Review
- Extramammary Paget's disease patient-derived xenografts harboring ERBB2 S310F mutation show sensitivity to HER2-targeted therapies.Oncogene · 2020Article
- Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance.Cancers · 2020Review
- [Pharmacological effects of site specific conjugated anti-human epidermal growth factor receptor 2-antibody drug conjugate using unnatural amino acid technology].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2019Article
- Article
- Targeting of the HER2/HER3 signaling axis overcomes ligand-mediated resistance to trastuzumab in HER2-positive breast cancer.Cancer medicine · 2019Article
- HER2 genomic amplification in circulating tumor DNA and estrogen receptor positivity predict primary resistance to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer.Breast cancer (Tokyo, Japan) · 2018Article
- Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.Oncotarget · 2018Article
- Current therapeutic landscape for advanced gastroesophageal cancers.Annals of translational medicine · 2018Review
- Chimeric antigen receptor T cells: a novel therapy for solid tumors.Journal of hematology & oncology · 2017Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOverexpression of heregulin, a HER3 ligand, is one mechanism that confers resistance to the anti-HER2 agents trastuzumab and lapatinib. We investigated the impact of heregulin expression on the efficacy of HER2-targeted therapeutic agents, including trastuzumab, trastuzumab emtansine (T-DM1) and lapatinib, in vitro and in vivo and evaluated the heregulin messenger RNA (mRNA) levels in specimens from patients with HER2-positive breast or gastric cancer.
resultsCell proliferation and apoptosis assays demonstrated that heregulin conferred robust resistance to lapatinib and trastuzumab via HER3-Akt pathway activation followed by survivin overexpression; however, heregulin conferred minimal or no resistance to T-DM1 and paclitaxel. The heregulin mRNA level of one of 10 patients was up-regulated after the acquisition of resistance to trastuzumab-based therapy. MATERIALS AND
methodsSK-BR-3, NCI-N87, BT-474, MDA-MB-453, HCC1954, SNU-216 and 4-1ST cells were pharmacologically treated with recombinant heregulin or transfected with the heregulin gene. We also assessed the expression of heregulin mRNA in HER2-positive breast or gastric cancer samples before and after trastuzumab-based therapy using a RT-PCR-based method.
conclusionsmRNA up-regulation of heregulin was observed in clinical breast cancer specimens during trastuzumab-based treatment, but heregulin overexpression had a limited effect on the sensitivity to T-DM1 in vitro and in vivo.
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