Trial reportCancer discovery2013
De-repression of PDGFRβ transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients.
Trial report in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 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
90 citing papers in PubMed, 141 citations in OpenAlex.
- Ex vivo drug screening and clustering of bladder cancers for pre-clinical treatment prediction.Communications medicine · 2026Article
- Endogenous inhibitors of PP2A activate oncogenic and DNA damage response kinases in glioblastoma.Cancer letters · 2026Article
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.International journal of molecular sciences · 2026Review
- Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Review
- Ascomycin enhances the antitumor activity of osimertinib in EGFR-TKI-resistant non-small cell lung cancer.Frontiers in oncology · 2026Article
- A PDGFRB-CD44-MIF crosstalk promotes cancer-associated cellular phenotypes in ATRT-TYR/MYC cell lines.Frontiers in oncology · 2026Article
- Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.Current oncology (Toronto, Ont.) · 2025Review
- Glioblastoma resistance to EGFR antibody-drug conjugate is driven by transcriptional reprogramming and TEK-induced EGFR suppression.Journal of translational medicine · 2025Article
- Comparative efficacy and safety of therapeutic strategies for EGFRvIII positive recurrent glioblastoma.iScience · 2025Article
- Identifying and exploiting combinatorial synthetic lethality by characterizing adaptive kinome rewiring of EGFRvIII-driven glioblastoma.Acta neuropathologica communications · 2025Article
- ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.Nature communications · 2025Article
- Targeting glioblastoma tumor hyaluronan to enhance therapeutic interventions that regulate metabolic cell properties.Advanced therapeutics · 2024Article
- Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling.Nature communications · 2024Article
- Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol.The oncologist · 2024Article
- Multiplex single-cell chemical genomics reveals the kinase dependence of the response to targeted therapy.Cell genomics · 2024Article
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- Abnormal glycosylation in glioma: related changes in biology, biomarkers and targeted therapy.Biomarker research · 2023Review
- Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.Frontiers in pharmacology · 2023Review
- EGFR, the Lazarus target for precision oncology in glioblastoma.Neuro-oncology · 2022Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 8 institutions in 2 countries.
Funding
Abstract
unlabelledAcquired resistance to tyrosine kinase inhibitors (TKI) represents a major challenge for personalized cancer therapy. Multiple genetic mechanisms of acquired TKI resistance have been identified in several types of human cancer. However, the possibility that cancer cells may also evade treatment by co-opting physiologically regulated receptors has not been addressed. Here, we show the first example of this alternate mechanism in brain tumors by showing that EGF receptor (EGFR)-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally de-repressing platelet-derived growth factor receptor β (PDGFRβ). Mechanistic studies show that EGFRvIII signaling actively suppresses PDGFRβ transcription in an mTORC1- and extracellular signal-regulated kinase-dependent manner. Genetic or pharmacologic inhibition of oncogenic EGFR renders GBMs dependent on the consequently de-repressed PDGFRβ signaling for growth and survival. Importantly, combined inhibition of EGFR and PDGFRβ signaling potently suppresses tumor growth in vivo. These data identify a novel, nongenetic TKI resistance mechanism in brain tumors and provide compelling rationale for combination therapy. SIGNIFICANCE: These results provide the fi rst clinical and biologic evidence for receptor tyrosinekinase (RTK) "switching" as a mechanism of resistance to EGFR inhibitors in GBM and provide a molecular explanation of how tumors can become "addicted" to a non amplified, nonmutated, physiologically regulated RTK to evade targeted treatment.
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.