ArticleCancer research2018
Combined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer.JCO precision oncology · 2022Pooled it
- Targeting MET and mTOR Synergistically Overcomes Adaptive Resistance in Glioblastoma.International journal of molecular sciences · 2026Article
- Exploring the landscape of targetable alterations in patients with glioblastoma.Nature reviews. Clinical oncology · 2026Review
- Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers.Nature communications · 2026Article
- Multiple patient-derived glioblastoma models reveal synthetic lethality through concurrent PI3K and CDK4/6 inhibition by blocking trans-active cooperation.Neuro-oncology · 2026Article
- SOX21 suppresses glioblastoma growth by repressing AP-1 activity.Cell death & disease · 2026Article
- Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis.Science advances · 2026Article
- BNIP3-mTOR Signaling Mediates Resistance to MET Inhibition in Glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- Abemaciclib impairs glioblastoma sphere formation by targeting the GSK3β-mediated transcriptional regulation of CD44 and TCF7L2.Cancer gene therapy · 2025Article
- The landscape of cyclin-dependent kinase 4/6 inhibitors in solid malignancies: emphasis on immunotherapy combinatorial strategies.Medical oncology (Northwood, London, England) · 2025Review
- CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.Journal of advanced research · 2025Article
- Treatment of a newly diagnosed glioblastoma harboring MET amplification with vebreltinib in combination with radiotherapy: a case report.Discover oncology · 2025Article
- Review
- c-Met inhibitor NVP-BVU972 induces antiviral protection and suppresses NF-κB-mediated inflammation.Frontiers in immunology · 2025Article
- Drug clinical trials on high-grade gliomas: challenges and hopes.Cancer biology & medicine · 2024Article
- SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the Hepatocellular Carcinoma Mouse Model.Current gene therapy · 2024Article
- Insights into the glioblastoma tumor microenvironment: current and emerging therapeutic approaches.Frontiers in pharmacology · 2024Review
- A novel c-Met/TRK inhibitor 1D228 efficiently inhibits tumor growth by targeting angiogenesis and tumor cell proliferation.Cell death & disease · 2023Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- Differences in metabolic transport and resistance mechanisms of Abemaciclib, Palbociclib, and Ribociclib.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Glioblastoma (GBM) is the most common primary brain malignancy and carries an extremely poor prognosis. Recent molecular studies revealed the CDK4/6-Rb-E2F axis and receptor tyrosine kinase (RTK) signaling to be deregulated in most GBM, creating an opportunity to develop more effective therapies by targeting both pathways. Using a phospho-RTK protein array, we found that both c-Met and TrkA-B pathways were significantly activated upon CDK4/6 inhibition in GBM cells. We therefore investigated the efficacy of combined CDK4/6 and c-Met/TrkA-B inhibition against GBM. We show that both c-Met and TrkA-B pathways transactivate each other, and targeting both pathways simultaneously results in more efficient pathway suppression. Mechanistically, inhibition of CDK4/6 drove NF-κB-mediated upregulation of hepatocyte growth factor, brain-derived neurotrophic factor, and nerve growth factor that in turn activated both c-Met and TrkA-B pathways. Combining the CDK4/6 inhibitor abemaciclib with the c-Met/Trk inhibitor altiratinib or the corresponding siRNAs induced apoptosis, leading to significant synergy against GBM. Collectively, these findings demonstrate that the activation of c-Met/TrkA-B pathways is a novel mechanism involved in therapeutic resistance of GBM to CDK4/6 inhibition and that dual inhibition of c-Met/Trk with CDK4/6 should be considered in future clinical trials.
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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.