ArticleNeuro-oncology2023
BH3 mimetics targeting BCL-XL impact the senescent compartment of pilocytic astrocytoma.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Trial
- MAPK-driven MYC/p21 axis controls senescence bypass and BCL-XL dependence in vincristine-resistant rhabdomyosarcoma.iScience · 2026Article
- Tempered optimism: Advances in the precision medicine era for pediatric low-grade glioma.Neuro-oncology · 2026Review
- Synergistic targeting of senolytic and senomorphic action with dual-engineered biomimetic macrophage nanovesicles for mitigating osteoarthritis.Bioactive materials · 2026Article
- Nested pediatric low-grade glioma cerebral organoid avatars reveal glutamatergic neuron stromal growth dependency.Genes & development · 2026Article
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- Revolutionizing cancer treatment with senotherapeutics: a current perspective.Cancer chemotherapy and pharmacology · 2026Review
- Article
- Navitoclax acts synergistically with irradiation to induce apoptosis in preclinical models of H3K27M-altered diffuse midline glioma.Scientific reports · 2025Article
- Multi-omics dissection of MAPK-driven senescence unveils therapeutic vulnerabilities in KIAA1549::BRAF-fusion pediatric low-grade glioma models.Signal transduction and targeted therapy · 2025Article
- Association of phosphorylation status of ERK and genetic MAPK alterations in pediatric tumors.Scientific reports · 2025Article
- HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells.Cell death and differentiation · 2025Article
- MOST wanted: navigating the MAPK-OIS-SASP-tumor microenvironment axis in primary pediatric low-grade glioma and preclinical models.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours.British journal of cancer · 2024Article
- Novel mitochondrial-related gene signature predicts prognosis and immunological status in glioma.Translational cancer research · 2024Article
- Review
- Rebound growth of BRAF mutant pediatric glioma cells after MAPKi withdrawal is associated with MAPK reactivation and secretion of microglia-recruiting cytokines.Journal of neuro-oncology · 2024Article
- A Conversation with ChatGPT on Contentious Issues in Senescence and Cancer Research.Molecular pharmacology · 2024Article
- Review
- Pediatric low-grade glioma: State-of-the-art and ongoing challenges.Neuro-oncology · 2024Review
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Authors and funding
28 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundPilocytic astrocytoma (PA) is the most common pediatric brain tumor and a mitogen-activated protein kinase (MAPK)-driven disease. Oncogenic MAPK-signaling drives the majority of cells into oncogene-induced senescence (OIS). While OIS induces resistance to antiproliferative therapies, it represents a potential vulnerability exploitable by senolytic agents.
methodsWe established new patient-derived PA cell lines that preserve molecular features of the primary tumors and can be studied in OIS and proliferation depending on expression or repression of the SV40 large T antigen. We determined expression of anti-apoptotic BCL-2 members in these models and primary PA. Dependence of senescent PA cells on anti-apoptotic BCL-2 members was investigated using a comprehensive set of BH3 mimetics.
resultsSenescent PA cells upregulate BCL-XL upon senescence induction and show dependency on BCL-XL for survival. BH3 mimetics with high affinity for BCL-XL (BCL-XLi) reduce metabolic activity and induce mitochondrial apoptosis in senescent PA cells at nano-molar concentrations. In contrast, BH3 mimetics without BCL-XLi activity, conventional chemotherapy, and MEK inhibitors show no effect.
conclusionsOur data demonstrate that BCL-XL is critical for survival of senescent PA tumor cells and provides proof-of-principle for the use of clinically available BCL-XL-dependent senolytics.
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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.