ArticleNature2013
Synthetic lethal metabolic targeting of cellular senescence in cancer therapy.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 317 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
317 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A bibliometric and visual analysis of the impact of senescence on tumor immunotherapy.Frontiers in immunology · 2025Pooled it
- Current hotspots and trends in cancer metabolic reprogramming: a scientometric analysis.Frontiers in immunology · 2024Pooled it
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Neonatal hyperoxia promotes macrophage senescence and lung injury via a p38MAPK-dependent secretome.American journal of respiratory cell and molecular biology · 2026Article
- Molecular mechanisms and recent advances in cellular senescence.Cell & bioscience · 2026Review
- Mitochondrial superoxide sustains a senescence-like phenotype in PARP- inhibited ovarian cancer cells by stabilizing HIF1α.Redox biology · 2026Article
- Advanced drug delivery platforms targeting cellular senescence: A promising strategy for cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Fatty acid channelling into triglycerides and oxylipins drives ferroptosis resistance during oncogenic BRAF-induced senescence.Cell death and differentiation · 2026Article
- Exploiting cellular senescence in hematologic malignancies.Translational oncology · 2026Review
- Autophagy revealed as a targetable vulnerability in senescent cells by cell painting phenotypic profiling: a mechanistic study of MCOPPB and related compounds.GeroScience · 2026Article
- Review
- The Emerging Role of Senolytics as a Next-Generation Strategy Against Glioma Recurrence: A Narrative Review.Cancers · 2026Review
- Article
- "Metabolic memory" of aging: anchoring, transmission, and frontiers of transgenerational intervention.Biogerontology · 2026Review
- Review
- The PARP inhibitor olaparib promotes senescence in murine macrophages.GeroScience · 2026Article
- Mitochondria-endoplasmic reticulum contact sites in hepatocytic senescence.Cellular & molecular biology letters · 2026Review
- Low hyper-oxygen exposure induces p21-dependent p53-independent senescence in alveolar cells.International journal of medical sciences · 2026Article
- Immunosenescence shapes the tumor immune microenvironment and limits PD-1/PD-L1 blockade efficacy in older patients with cancer.Frontiers in immunology · 2026Review
257 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activated oncogenes and anticancer chemotherapy induce cellular senescence, a terminal growth arrest of viable cells characterized by S-phase entry-blocking histone 3 lysine 9 trimethylation (H3K9me3). Although therapy-induced senescence (TIS) improves long-term outcomes, potentially harmful properties of senescent tumour cells make their quantitative elimination a therapeutic priority. Here we use the Eµ-myc transgenic mouse lymphoma model in which TIS depends on the H3K9 histone methyltransferase Suv39h1 to show the mechanism and therapeutic exploitation of senescence-related metabolic reprogramming in vitro and in vivo. After senescence-inducing chemotherapy, TIS-competent lymphomas but not TIS-incompetent Suv39h1(-) lymphomas show increased glucose utilization and much higher ATP production. We demonstrate that this is linked to massive proteotoxic stress, which is a consequence of the senescence-associated secretory phenotype (SASP) described previously. SASP-producing TIS cells exhibited endoplasmic reticulum stress, an unfolded protein response (UPR), and increased ubiquitination, thereby targeting toxic proteins for autophagy in an acutely energy-consuming fashion. Accordingly, TIS lymphomas, unlike senescence models that lack a strong SASP response, were more sensitive to blocking glucose utilization or autophagy, which led to their selective elimination through caspase-12- and caspase-3-mediated endoplasmic-reticulum-related apoptosis. Consequently, pharmacological targeting of these metabolic demands on TIS induction in vivo prompted tumour regression and improved treatment outcomes further. These findings unveil the hypercatabolic nature of TIS that is therapeutically exploitable by synthetic lethal metabolic targeting.
Indexed as
Identifiers
23945590What OpenQuestion holds
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.