ArticleNeuro-oncology2025
Designing a time-dependent therapeutic strategy using CDK4/6 inhibitors in an intracranial ATRT model.
Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A Phase Ib Case Series Using Bortezomib With Chemotherapy in Atypical Teratoid/Rhabdoid Tumors.Cancer medicine · 2026Article
- Aggressive atypical teratoid/rhabdoid tumor with extensive leptomeningeal metastasis in an 8-year-old boy: a case report and narrative review.Translational pediatrics · 2026Article
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Authors and funding
11 authors.
Funding
Abstract
backgroundInhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6), crucial for cell cycle regulation, have shown promise in early-stage studies for treating central nervous system (CNS) tumors. However, challenges such as limited CNS penetration, optimal treatment duration, and systemic side effects have impeded their clinical translation for pediatric brain tumors (PBTs).
methodsWe evaluated the potency of CDK4/6 inhibitors across various PBT cell lines, focusing particularly on palbociclib against atypical teratoid rhabdoid tumor (ATRT) with cell viability assays and gene expression analysis. Additionally, we assessed the efficacy and safety of intrathecal (IT) delivery of palbociclib through neurotoxicity and pharmacokinetic studies, along with survival assessments in murine leptomeningeal ATRT models.
resultsPalbociclib showed the highest potency across various PBT cells, with extended treatments reducing growth inhibition 50 (GI50) values from the micromolar to nanomolar range. It suppressed critical cell cycle genes (CCNB1, CCNA2, CDK1) in BT16 ATRT cells. Neurotoxicity (GFAP, CD45, NeuN, Iba1) and pharmacokinetic assays confirmed IT route as a feasible and effective method for delivering palbociclib to the cerebrospinal fluid (CSF), avoiding systemic toxicity and enhancing drug concentration to the brain. Finally, metronomic IT delivery using an osmotic pump (OP, 48 mg/kg) increased survival in 2 murine leptomeningeal ATRT models, showcasing its potential as a novel therapy for leptomeningeal tumors.
conclusionsMetronomic IT delivery of palbociclib enhances drug efficacy and safety, improves survival, and offers a promising treatment strategy for PBTs with CSF dissemination.
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