ArticleProceedings of the National Academy of Sciences of the United States of America2006
Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 250 papers, 1 of them a synthesis that pooled it.
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
250 citing papers in PubMed, 1 synthesis or guideline pooled it, 482 citations in OpenAlex.
- Prognostic value of c-Met in colorectal cancer: a meta-analysis.World journal of gastroenterology · 2015Pooled it
- Biomarker analyses from a placebo-controlled phase II study evaluating erlotinib±onartuzumab in advanced non-small cell lung cancer: MET expression levels are predictive of patient benefit.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Trial
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- PTEN loss and ERBB2/ERBB3-mediated AKT reactivation drive resistance to MET inhibition in MET-amplified hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- MET Alterations in Cancer and MET-Targeted Therapy: Detection Strategies, Treatment Efficacy, and Emerging Technologies.Targeted oncology · 2025Review
- E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network.Cancer research communications · 2024Article
- MET Oncogene Targeting for Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- The MET Oncogene: Thirty Years of Insights into Molecular Mechanisms Driving Malignancy.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Targeting MET in NSCLC: An Ever-Expanding Territory.JTO clinical and research reports · 2024Review
- Receptor tyrosine kinase gene expression profiling of orbital rhabdomyosarcoma unveils MET as a potential biomarker and therapeutic target.Human cell · 2024Article
- Review
- Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer.Science advances · 2023Article
- MET exon 14 skipping mutation is a hepatocyte growth factor (HGF)-dependent oncogenic driver in vitro and in humanised HGF knock-in mice.Molecular oncology · 2023Article
- Tyrosine kinase signaling-independent MET-targeting with CAR-T cells.Journal of translational medicine · 2023Article
- A consolidated working classification of gastric cancer for histopathologists (Review).Biomedical reports · 2023Review
- Epithelial cell adhesion molecule (EpCAM) regulates HGFR signaling to promote colon cancer progression and metastasis.Journal of translational medicine · 2023Article
- Switchable DNA Catalysts for Proximity Labeling at Sites of Protein-Protein Interactions.Journal of the American Chemical Society · 2023Article
- Dramatic Response to Cabozantinib in a Patient with Refractory Hepatocellular Carcinoma with c-Journal of clinical and translational hepatology · 2023Article
- Preclinical Characterization of XL092, a Novel Receptor Tyrosine Kinase Inhibitor of MET, VEGFR2, AXL, and MER.Molecular cancer therapeutics · 2023Article
190 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The success of molecular targeted therapy in cancer may depend on the selection of appropriate tumor types whose survival depends on the drug target, so-called "oncogene addiction." Preclinical approaches to defining drug-responsive subsets are needed if initial clinical trials are to be directed at the most susceptible patient population. Here, we show that gastric cancer cells with high-level stable chromosomal amplification of the growth factor receptor MET are extraordinarily susceptible to the selective inhibitor PHA-665752. Although MET activation has primarily been linked with tumor cell migration and invasiveness, the amplified wild-type MET in these cells is constitutively activated, and its continued signaling is required for cell survival. Treatment with PHA-665752 triggers massive apoptosis in 5 of 5 gastric cancer cell lines with MET amplification but in 0 of 12 without increased gene copy numbers (P = 0.00016). MET amplification may thus identify a subset of epithelial cancers that are uniquely sensitive to disruption of this pathway and define a patient group that is appropriate for clinical trials of targeted therapy using MET inhibitors.
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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.