ArticleOncogene2013
A novel bispecific EGFR/Met antibody blocks tumor-promoting phenotypic effects induced by resistance to EGFR inhibition and has potent antitumor activity.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 61 citations in OpenAlex.
- DNA-programmed bispecific peptide assemblies for delivering cytotoxic payload to cells expressing EGFR and MET receptors.RSC chemical biology · 2026Article
- Antibody Drug Conjugates (ADCs): Shaping the Future of Precision Oncology.Anti-cancer agents in medicinal chemistry · 2025Review
- Unlocking the potential of bispecific ADCs for targeted cancer therapy.Frontiers of medicine · 2024Review
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Targeting lung cancer with clinically relevant EGFR mutations using anti-EGFR RNA aptamer.Molecular therapy. Nucleic acids · 2023Article
- Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer.Therapeutic advances in medical oncology · 2022Review
- A receptor-antibody hybrid hampering MET-driven metastatic spread.Journal of experimental & clinical cancer research : CR · 2021Article
- Oncogenic mechanism-based pharmaceutical validation of therapeutics targeting MET receptor tyrosine kinase.Therapeutic advances in medical oncology · 2021Review
- Bispecific antibodies targeting dual tumor-associated antigens in cancer therapy.Journal of cancer research and clinical oncology · 2020Review
- Bispecific Antibodies and Antibody-Drug Conjugates for Cancer Therapy: Technological Considerations.Biomolecules · 2020Review
- Proximity proteomics identifies cancer cell membrane cis-molecular complex as a potential cancer target.Cancer science · 2019Article
- Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics.Molecular medicine (Cambridge, Mass.) · 2018Review
- A phase I study of LY3164530, a bispecific antibody targeting MET and EGFR, in patients with advanced or metastatic cancer.Cancer chemotherapy and pharmacology · 2018Article
- Article
- Bi-specific molecule against EGFR and death receptors simultaneously targets proliferation and death pathways in tumors.Scientific reports · 2017Article
- Article
- Cancer Transcriptome Dataset Analysis: Comparing Methods of Pathway and Gene Regulatory Network-Based Cluster Identification.Omics : a journal of integrative biology · 2017Article
- The impact of MET, IGF-1, IGF1R expression and EGFR mutations on survival of patients with non-small-cell lung cancer.PloS one · 2017Article
- Article
- Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment.Trends in pharmacological sciences · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Simultaneous targeting of epidermal growth factor receptor (EGFR) and Met in cancer therapy is under pre-clinical and clinical evaluation. Here, we report the finding that treatment with EGFR inhibitors of various tumor cells, when stimulated with hepatocyte growth factor (HGF) and EGF, results in transient upregulation of phosphorylated AKT. Furthermore, EGFR inhibition in this setting stimulates a pro-invasive phenotype as assessed in Matrigel-based assays. Simultaneous treatment with AKT and EGFR inhibitors abrogates this invasive growth, hence functionally linking signaling and phenotype. This observation implies that during treatment of tumors a balanced ratio of EGFR and Met inhibition is required. To address this, we designed a bispecific antibody targeting EGFR and Met, which has the advantage of a fixed 2:1 stoichiometry. This bispecific antibody inhibits proliferation in tumor cell cultures and co-cultures with fibroblasts in an additive manner compared with treatment with both single agents. In addition, cell migration assays reveal a higher potency of the bispecific antibody in comparison with the antibodies' combination at low doses. We demonstrate that the bispecific antibody inhibits invasive growth, which is specifically observed with cetuximab. Finally, the bispecific antibody potently inhibits tumor growth in a non-small cell lung cancer xenograft model bearing a strong autocrine HGF-loop. Together, our findings strongly support a combination treatment of EGFR and Met inhibitors and further evaluation of resistance mechanisms to EGFR inhibition in the context of active Met signaling.
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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.