ArticleCancer biology & therapy2014
PDE5 inhibitors enhance the lethality of standard of care chemotherapy in pediatric CNS tumor cells.
Article in Cancer biology & therapy, 2014. 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
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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
34 citing papers in PubMed, 47 citations in OpenAlex.
- The pivotal role of autophagy in the pathogenesis and therapy of medulloblastoma.Future oncology (London, England) · 2024Review
- Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma.medRxiv : the preprint server for health sciences · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- The recent progress of myeloid-derived suppressor cell and its targeted therapies in cancers.MedComm · 2023Review
- How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme.Pharmacological reports : PR · 2022Review
- Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Tadalafil in Colorectal Cancer.Frontiers in pharmacology · 2022Article
- Myeloid-derived suppressor cells (MDSCs) in brain cancer: challenges and therapeutic strategies.Inflammopharmacology · 2021Review
- Role of phosphodiesterase 1 in the pathophysiology of diseases and potential therapeutic opportunities.Pharmacology & therapeutics · 2021Review
- Review
- Hydrogen peroxide induces nucleus pulposus cell apoptosis by ATF4/CHOP signaling pathway.Experimental and therapeutic medicine · 2020Article
- New drugs are not enough‑drug repositioning in oncology: An update.International journal of oncology · 2020Review
- Clinical Perspective of FDA Approved Drugs With P-Glycoprotein Inhibition Activities for Potential Cancer Therapeutics.Frontiers in oncology · 2020Review
- Phosphodiesterase Type 5 Inhibitors Synergize Vincristine in Killing Castration-Resistant Prostate Cancer Through Amplifying Mitotic Arrest Signaling.Frontiers in oncology · 2020Article
- Advantages of Phosphodiesterase Type 5 Inhibitors in the Management of Glucose Metabolism Disorders: A Clinical and Translational Issue.International journal of endocrinology · 2020Review
- Activation of the cGMP/protein kinase G system in breast cancer by the dopamine receptor-1.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Chemical modulation of autophagy as an adjunct to chemotherapy in childhood and adolescent brain tumors.Oncotarget · 2018Review
- Role of the unfolded protein response in determining the fate of tumor cells and the promise of multi-targeted therapies.Cell stress & chaperones · 2018Review
- Repurposing drugs in oncology (ReDO)-selective PDE5 inhibitors as anti-cancer agents.Ecancermedicalscience · 2018Article
- Curcumin interacts with sildenafil to kill GI tumor cells via endoplasmic reticulum stress and reactive oxygen/ nitrogen species.Oncotarget · 2017Article
- Phosphodiesterase type 5 and cancers: progress and challenges.Oncotarget · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
We determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with clinically relevant chemotherapies to kill medulloblastoma cells. In medulloblastoma cells PDE5 inhibitors interacted in a greater than additive fashion with vincristine/etoposide/cisplatin to cause cell death. Knockdown of PDE5 expression recapitulated the combination effects of PDE5 inhibitor drugs with chemotherapy drugs. Expression of dominant negative caspase 9 did not significantly inhibit chemotherapy lethality but did significantly reduce enhanced killing in combination with the PDE5 inhibitor sildenafil. Overexpression of BCL-XL and c-FLIP-s suppressed individual and combination drug toxicities. Knockdown of CD95 or FADD suppressed drug combination toxicity. Treatment with PDE5 inhibitors and chemotherapy drugs promoted autophagy which was maximal at ~12 h post-treatment, and in a cell type-dependent manner knockdown of Beclin1 or ATG5 either suppressed or enhanced drug combination lethality. PDE5 inhibitors enhanced the induction of chemotherapy-induced DNA damage in a nitric oxide synthase-dependent fashion. In conclusion, our data demonstrate that the combination of PDE5 inhibitors with standard of care chemotherapy agents for medulloblastoma represents a possible novel modality for future treatment of this disease.
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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.