ArticleNature communications2020
Modeling germline mutations in pineoblastoma uncovers lysosome disruption-based therapy.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies.Cancer cell · 2026Article
- Modeling pediatric brain tumors with human stem cells.Frontiers in cellular neuroscience · 2026Review
- Nortriptyline Inhibits Lysosomal Exocytosis-Mediated SASP During Gastric Cancer Progression via Targeting HOXA1-PITX2 Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Development and Validation of Survival Prediction Models for Patients With Pineoblastomas Using Deep Learning: A SEER-Based Study.Cancer reports (Hoboken, N.J.) · 2025Article
- An imbalance between proliferation and differentiation underlies the development of microRNA-defective pineoblastoma.Genes & development · 2025Article
- Drosha: a new tumor suppressor in pineoblastoma.Genes & development · 2025Article
- Beyond the brain: exploring the impact of animal models of leptomeningeal disease from solid tumors.Acta neuropathologica communications · 2025Review
- Review
- Recent Advances in Pineoblastoma Research: Molecular Classification, Modelling and Targetable Vulnerabilities.Cancers · 2025Review
- SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors.Neuro-oncology · 2024Review
- Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway.Scientific reports · 2024Article
- The first pineoblastoma case report of a patient with Sotos syndrome harboring NSD1 germline mutation.BMC pediatrics · 2024Article
- Antidepressants as Autophagy Modulators for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Pineal/germ cell tumors and pineal parenchymal tumors.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2023Review
- Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer.Nature communications · 2023Article
- A temporal in vivo catalog of chromatin accessibility and expression profiles in pineoblastoma reveals a prevalent role for repressor elements.Genome research · 2023Article
- Advances in the Treatment of Pediatric Brain Tumors.Children (Basel, Switzerland) · 2022Review
- Repurposing autophagy regulators in brain tumors.International journal of cancer · 2022Review
- Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study.Acta neuropathologica · 2021Article
Corrections and comments
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Authors and funding
21 authors at 8 institutions in 4 countries.
Funding
Abstract
Pineoblastoma is a rare pediatric cancer induced by germline mutations in the tumor suppressors RB1 or DICER1. Presence of leptomeningeal metastases is indicative of poor prognosis. Here we report that inactivation of Rb plus p53 via a WAP-Cre transgene, commonly used to target the mammary gland during pregnancy, induces metastatic pineoblastoma resembling the human disease with 100% penetrance. A stabilizing mutation rather than deletion of p53 accelerates metastatic dissemination. Deletion of Dicer1 plus p53 via WAP-Cre also predisposes to pineoblastoma, albeit with lower penetrance. In silico analysis predicts tricyclic antidepressants such as nortriptyline as potential therapeutics for both pineoblastoma models. Nortriptyline disrupts the lysosome, leading to accumulation of non-functional autophagosome, cathepsin B release and pineoblastoma cell death. Nortriptyline further synergizes with the antineoplastic drug gemcitabine to effectively suppress pineoblastoma in our preclinical models, offering new modality for this lethal childhood malignancy.
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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.