ArticleMolecular cancer2014
Trastuzumab emtansine is active on HER-2 overexpressing NSCLC cell lines and overcomes gefitinib resistance.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 67 citations in OpenAlex.
- Trastuzumab and paclitaxel in patients with EGFR mutated NSCLC that express HER2 after progression on EGFR TKI treatment.British journal of cancer · 2018Trial
- Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer.Scientific reports · 2025Article
- Effects of trastuzumab emtansine on canine osteosarcoma cells.The Journal of veterinary medical science · 2025Article
- Article
- Trastuzumab-Emtansine and Osimertinib Combination Therapy to TargetJTO clinical and research reports · 2023Article
- Ado-tratuzumab emtansine beyond breast cancer: therapeutic role of targeting other HER2-positive cancers.Frontiers in molecular biosciences · 2023Review
- Association betweenAnnals of translational medicine · 2022Article
- Focusing on NK cells and ADCC: A promising immunotherapy approach in targeted therapy for HER2-positive breast cancer.Frontiers in immunology · 2022Review
- Activity of trastuzumab emtansine (T-DM1) in 3D cell culture.Breast cancer research and treatment · 2021Article
- Lipidated Peptidomimetic Ligand-Functionalized HER2 Targeted Liposome as Nano-Carrier Designed for Doxorubicin Delivery in Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Progress in Treatment of Non-Small Cell Lung Cancer Harboring HER2 Aberrations.OncoTargets and therapy · 2021Review
- Combined Small and Squamous Transformation in EGFR-mutated Lung Adenocarcinoma.Internal medicine (Tokyo, Japan) · 2020Article
- Osimertinib for Front-Line Treatment of Locally Advanced or MetastaticCancer management and research · 2020Review
- Article
- Pre-treatment with the CDK4/6 inhibitor palbociclib improves the efficacy of paclitaxel in TNBC cells.Scientific reports · 2019Article
- Transcriptomic study of the mechanism of anoikis resistance in head and neck squamous carcinoma.PeerJ · 2019Article
- The Properties of Cysteine-Conjugated Antibody-Drug Conjugates Are Impacted by the IgG Subclass.The AAPS journal · 2018Article
- Esophageal cancer cells resistant to T-DM1 display alterations in cell adhesion and the prostaglandin pathway.Oncotarget · 2018Article
- The anti-tumor efficacy of CDK4/6 inhibition is enhanced by the combination with PI3K/AKT/mTOR inhibitors through impairment of glucose metabolism in TNBC cells.Journal of experimental & clinical cancer research : CR · 2018Article
- EGFR-TKIs resistance via EGFR-independent signaling pathways.Molecular cancer · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHER-2 represents a relatively new therapeutic target for non small cell lung cancer (NSCLC) patients. The incidence for reported HER-2 overexpression/amplification/mutations ranges from 2 to 20% in NSCLC. Moreover, HER-2 amplification is a potential mechanism of resistance to tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) (about 10% of cases). T-DM1, trastuzumab emtansine is an antibody-drug conjugate composed by the monoclonal antibody trastuzumab and the microtubule polymerization inhibitor DM1. The activity of T-DM1 has been studied in breast cancer but the role of T-DM1 in lung cancer remains unexplored.
methodsAntiproliferative and proapoptotic effects of T-DM1 have been investigated in different NSCLC cell lines by MTT, crystal violet staining, morphological study and Western blotting. HER-2 expression and cell cycle were evaluated by flow cytometry and Western blotting. Antibody dependent cell cytotoxicity (ADCC) was measured with a CytoTox assay. Xenografted mice model has been generated using a NSCLC cell line to evaluate the effect of T-DM1 on tumor growth. Moreover, a morphometric and immunohistochemical analysis of tumor xenografts was conducted.
resultsIn this study we investigated the effect of T-DM1 in a panel of NSCLC cell lines with different HER-2 expression levels, in H1781 cell line carrying HER-2 mutation and in gefitinib resistant HER-2 overexpressing PC9/HER2cl1 cell clone. T-DM1 efficiently inhibited proliferation with arrest in G2-M phase and induced cell death by apoptosis in cells with a significant level of surface expression of HER-2. Antibody-dependent cytotoxicity assay documented that T-DM1 maintained the same activity of trastuzumab. Our data also suggest that targeting HER-2 with T-DM1 potentially overcomes gefitinib resistance. In addition a correlation between cell density/tumor size with both HER-2 expression and T-DM1 activity was established in vitro and in an in vivo xenograft model.
conclusionsOur results indicate that targeting HER-2 with T-DM1 may offer a new therapeutic approach in HER-2 over-expressing lung cancers including those resistant to EGFR TKIs.
Indexed as
Identifiers
What 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.