ArticleNature communications2019
Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 147 papers, 1 of them a synthesis that pooled it.
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
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 212 citations in OpenAlex.
- Senogenic-senolytic treatment strategies enhance tumor control and can improve survival in murine cancer models: a systematic review.BMC cancer · 2026Pooled it
- Evaluating carboplatin and PARP inhibitor combination efficacy using high-grade serous carcinoma spheroids and organoids.Cancer biology & therapy · 2026Article
- Novel Flavonoid Senotherapeutics Identified by Phenotypic Drug Discovery Reduce Senescence and Improve Multiple Markers of Healthspan.Aging cell · 2026Article
- CD73 inhibition overcomes adaptive immune resistance to PARP inhibition in models of prostate cancer.The Journal of clinical investigation · 2026Article
- Werner helicase inhibitor for advanced microsatellite instability solid tumors: a phase 1 trial.Nature medicine · 2026Article
- BCLXSignal transduction and targeted therapy · 2026Article
- Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy.Biogerontology · 2026Review
- Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular Senescence.Molecular carcinogenesis · 2026Article
- The Bidirectional Role of Cellular Senescence in the Treatment of Ovarian Cancer.Biomedicines · 2026Review
- Fibrillarin Resists Cellular Senescence Via SIRT1-Dependent Nicotinamide Metabolism and Its Inhibition Sensitizes Senolytic Therapy in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Natural products targeting cytokine-regulated SASP inflammation networks in Ovarian cancer: Implications on immune escape and molecular resistance.Inflammopharmacology · 2026Review
- PARP inhibitors induce a senescence phenotype in non-small cell lung carcinoma cell lines.FEBS open bio · 2026Article
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells.Cell death & disease · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Mitochondrial superoxide sustains a senescence-like phenotype in PARP- inhibited ovarian cancer cells by stabilizing HIF1α.Redox biology · 2026Article
- Article
- Disproportionality Analysis of Hematologic Adverse Event Signals Associated with Venetoclax in Combination with Senescence-Inducing Chemotherapy.Journal of clinical medicine · 2026Article
- Molecular profiling of glioblastoma-derived extracellular vesicles identifies small nucleolar RNAs as candidate liquid biomarkers for radiation- induced senescence.bioRxiv : the preprint server for biology · 2026Article
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Senescence is a tumor suppression mechanism defined by stable proliferation arrest. Here we demonstrate that the known synthetic lethal interaction between poly(ADP-ribose) polymerase 1 inhibitors (PARPi) and DNA repair triggers p53-independent ovarian cancer cell senescence defined by senescence-associated phenotypic hallmarks including DNA-SCARS, inflammatory secretome, Bcl-XL-mediated apoptosis resistance, and proliferation restriction via Chk2 and p21 (CDKN1A). The concept of senescence as irreversible remains controversial and here we show that PARPi-senescent cells re-initiate proliferation upon drug withdrawal, potentially explaining the requirement for sustained PARPi therapy in the clinic. Importantly, PARPi-induced senescence renders ovarian and breast cancer cells transiently susceptible to second-phase synthetic lethal approaches targeting the senescence state using senolytic drugs. The combination of PARPi and a senolytic is effective in preclinical models of ovarian and breast cancer suggesting that coupling these synthetic lethalities provides a rational approach to their clinical use and may together be more effective in limiting resistance.
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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.