ArticleNature communications2021
Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 27 citations in OpenAlex.
- Osteosarcoma Across the Age Spectrum: Why Outcomes Diverge and Trials Must Adapt.Journal of clinical medicine · 2026Review
- A tailored in vivo CRISPR screen identifies BAP1 as a potent tumor suppressor of sarcoma.JCI insight · 2026Article
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- FBXL5 depletion as a novel strategy against osteosarcoma: Evidence for MEK/ERK inhibition and enhanced therapeutic sensitivity.Oncology letters · 2026Article
- Understanding and Overcoming Osteosarcoma Heterogeneity.Biomolecules · 2026Review
- Review
- From Bench to Bedside: Advancements in Precision Oncology and Drug Discovery for Osteosarcoma.Cancers · 2026Review
- Age-Stratified Transcriptomic Profiling Reveals Biologically Distinct Molecular Phenotypes Across Pediatric, Adolescent, and Adult Osteosarcoma.Biomedicines · 2026Article
- RB1-I680T mutation potentiates tumor growth and chemotherapy sensitivity in non-small cell lung cancer via derepressing E2F1 transcription.Cell communication and signaling : CCS · 2026Article
- Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer.iScience · 2026Review
- PARP inhibitors across different malignancies: clinical applications, resistance mechanisms, and strategies to enhance efficacy through combination therapies.Frontiers in cell and developmental biology · 2026Review
- The effect of postoperative chemotherapy on survival outcomes and a nomogram for predicting overall survival in chondroblastic osteosarcoma.Scientific reports · 2025Article
- Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer.Cancers · 2025Review
- High-grade glioma with pleomorphic and pseudopapillary features: a single-institution series of three cases.Acta neuropathologica communications · 2025Article
- Identification of Nogo-B as a potential therapeutic target of osteosarcoma via stereochemically selective covalent probes.Cell death & disease · 2025Article
- Targeting metastasis in paediatric bone sarcomas.Molecular cancer · 2025Review
- Genetic profiling of osteosarcoma in an adolescent using a next‑generation sequencing panel and Sanger sequencing: A case report and review of the literature.Biomedical reports · 2025Article
- Biomimetic Targeted Co-Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Disclosure of Potential Therapeutic Targets in Plumbagin for Treating Osteosarcoma.Biomedical engineering and computational biology · 2025Article
- PDK1, associated with glycolytic metabolism, is a potential prognostic biomarker in osteosarcoma.PloS one · 2025Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 3 countries.
Funding
Abstract
Loss-of-function mutations in the RB1 tumour suppressor are key drivers in cancer, including osteosarcoma. RB1 loss-of-function compromises genome-maintenance and hence could yield vulnerability to therapeutics targeting such processes. Here we demonstrate selective hypersensitivity to clinically-approved inhibitors of Poly-ADP-Polymerase1,2 inhibitors (PARPi) in RB1-defective cancer cells, including an extended panel of osteosarcoma-derived lines. PARPi treatment results in extensive cell death in RB1-defective backgrounds and prolongs survival of mice carrying human RB1-defective osteosarcoma grafts. PARPi sensitivity is not associated with canonical homologous recombination defect (HRd) signatures that predict PARPi sensitivity in cancers with BRCA1,2 loss, but is accompanied by rapid activation of DNA replication checkpoint signalling, and active DNA replication is a prerequisite for sensitivity. Importantly, sensitivity in backgrounds with natural or engineered RB1 loss surpasses that seen in BRCA-mutated backgrounds where PARPi have established clinical benefit. Our work provides evidence that PARPi sensitivity extends beyond cancers identifiable by HRd and advocates PARP1,2 inhibition as a personalised strategy for RB1-mutated osteosarcoma and other cancers.
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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.