ArticleNeuro-oncology2022
A novel PLK1 inhibitor onvansertib effectively sensitizes MYC-driven medulloblastoma to radiotherapy.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Potent synthetic lethality between PLK1 and EYA family inhibitors in tumors of the central and peripheral nervous systems.Genes & development · 2026Article
- Targeting PLK1 Reduces MMP10 to Enhance Radiosensitivity in HPV- Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Targeting PLK1 potentiates the antitumor efficacy of EGFR-TKIs through inhibiting the JAK1/STAT3 pathway.Cell death & disease · 2026Article
- Transcriptional regulation of protein synthesis by mediator kinase represents a therapeutic vulnerability in MYC-driven medulloblastoma.Nature communications · 2025Article
- The dual HDAC/PI3K inhibitor CUDC-907 inhibits the growth and proliferation of MYC-driven Group 3 medulloblastoma.Cell death discovery · 2025Article
- MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma.Neuro-oncology · 2025Article
- PLK1 in cancer therapy: a comprehensive review of immunomodulatory mechanisms and therapeutic opportunities.Frontiers in immunology · 2025Review
- Onvansertib exhibits anti-proliferative and anti-invasive effects in endometrial cancer.Frontiers in pharmacology · 2025Article
- Rethinking MYC inhibition: a multi-dimensional approach to overcome cancer's master regulator.Frontiers in cell and developmental biology · 2025Review
- Onvansertib inhibits cell proliferation and increases sensitivity to paclitaxel in uterine serous cancer cells.American journal of cancer research · 2025Article
- The effect of deuterated PLK1 inhibitor on its safety and efficacyFrontiers in oncology · 2025Article
- AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer.Molecular cancer therapeutics · 2024Article
- NOD2 reduces the chemoresistance of melanoma by inhibiting the TYMS/PLK1 signaling axis.Cell death & disease · 2024Article
- Proteogenomic characterization of skull-base chordoma.Nature communications · 2024Article
- Onvansertib treatment overcomes olaparib resistance in high-grade ovarian carcinomas.Cell death & disease · 2024Article
- Multifunctional Fluoropolymer-Engineered Magnetic Nanoparticles to Facilitate Blood-Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- AVERON notebook to discover actionable cancer vulnerabilities enabled by neomorph protein-protein interactions.iScience · 2024Article
- The pivotal role of irradiation-induced apoptosis in the pathogenesis and therapy of medulloblastoma.Cancer reports (Hoboken, N.J.) · 2024Review
- The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGroup 3 medulloblastoma (MB) is often accompanied by MYC amplification. PLK1 is an oncogenic kinase that controls cell cycle and proliferation and has been preclinically validated as a cancer therapeutic target. Onvansertib (PCM-075) is a novel, orally available PLK1 inhibitor, which shows tumor growth inhibition in various types of cancer. We aim to explore the effect of onvansertib on MYC-driven medulloblastoma as a monotherapy or in combination with radiation.
methodsCrisper-Cas9 screen was used to discover essential genes for MB tumor growth. Microarray and immunohistochemistry on pediatric patient samples were performed to examine the expression of PLK1. The effect of onvansertib in vitro was measure by cell viability, colony-forming assays, extreme limiting dilution assay, and RNA-Seq. ALDH activity, cell-cycle distribution, and apoptosis were analyzed by flow cytometry. DNA damage was assessed by immunofluorescence staining. Medulloblastoma xenografts were generated to explore the monotherapy or radio-sensitizing effect.
resultsPLK1 is overexpressed in Group 3 MB. The IC50 concentrations of onvansertib in Group 3 MB cell lines were in a low nanomolar range. Onvansertib reduced colony formation, cell proliferation, stem cell renewal and induced G2/M arrest in vitro. Moreover, onvansertib in combination with radiation increased DNA damage and apoptosis compared with radiation treatment alone. The combination radiotherapy resulted in marked tumor regression in xenografts.
conclusionsThese findings demonstrate the efficacy of a novel PLK1 inhibitor onvansertib in vitro and in xenografts of Group 3 MB, which suggests onvansertib is an effective strategy as monotherapy or in combination with radiotherapy in MB.
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