ArticleCancer research2020
Cooperative Blockade of PKCα and JAK2 Drives Apoptosis in Glioblastoma.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Review
- PKCα Activation via the Thyroid Hormone Membrane Receptor Is Key to Thyroid Cancer Growth.International journal of molecular sciences · 2024Article
- IL-6/JAK2-dependent G6PD phosphorylation promotes nucleotide synthesis and supports tumor growth.Molecular metabolism · 2023Article
- From signalling pathways to targeted therapies: unravelling glioblastoma's secrets and harnessing two decades of progress.Signal transduction and targeted therapy · 2023Review
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Glioblastoma: Current Status, Emerging Targets, and Recent Advances.Journal of medicinal chemistry · 2022Review
- Transcriptomics-Based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma Cells.Cancers · 2021Article
- Targeting Protein Kinase C in Glioblastoma Treatment.Biomedicines · 2021Review
- Review
- Evaluation of the antitumor effects of PP242 in a colon cancer xenograft mouse model using comprehensive metabolomics and lipidomics.Scientific reports · 2020Article
- Bioinformatics Analysis Discovers Microtubular Tubulin Beta 6 Class V (TUBB6) as a Potential Therapeutic Target in Glioblastoma.Frontiers in genetics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The mTOR signaling is dysregulated prominently in human cancers including glioblastoma, suggesting mTOR as a robust target for therapy. Inhibitors of mTOR have had limited success clinically, however, in part because their mechanism of action is cytostatic rather than cytotoxic. Here, we tested three distinct mTOR kinase inhibitors (TORKi) PP242, KU-0063794, and sapanisertib against glioblastoma cells. All agents similarly decreased proliferation of glioblastoma cells, whereas PP242 uniquely induced apoptosis. Apoptosis induced by PP242 resulted from off-target cooperative inhibition of JAK2 and protein kinase C alpha (PKCα). Induction of apoptosis was also decreased by additional on-target inhibition of mTOR, due to induction of autophagy. As EGFR inhibitors can block PKCα, EGFR inhibitors erlotinib and osimertinib were tested separately in combination with the JAK2 inhibitor AZD1480. Combination therapy induced apoptosis of glioblastoma tumors in both flank and in patient-derived orthotopic xenograft models, providing a preclinical rationale to test analogous combinations in patients. SIGNIFICANCE: These findings identify PKCα and JAK2 as targets that drive apoptosis in glioblastoma, potentially representing a clinically translatable approach for glioblastoma.
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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.