ArticleNature2015
Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 336 papers.
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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
336 citing papers in PubMed, 589 citations in OpenAlex.
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- Self-driven electrical triggering system activates tunneling nanotube highways to enhance drug delivery in bladder cancer therapy.Nature communications · 2025Article
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- One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer.Cell death discovery · 2025Article
- Proteogenomic characterization unveils biomarkers associated with chemoresistance in muscle-invasive bladder cancer.Cell reports. Medicine · 2025Article
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- Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms.Biochemical genetics · 2025Article
- Immunoregulatory mechanisms of the arachidonic acid pathway in cancer.FEBS letters · 2025Review
- Advanced hierarchical computational modeling-based rational development of platinum (II) nanocomplex to improve lung cancer therapy.Advanced functional materials · 2025Article
- Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
276 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Cytotoxic chemotherapy is effective in debulking tumour masses initially; however, in some patients tumours become progressively unresponsive after multiple treatment cycles. Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to repopulate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation. This repopulation can be abrogated by a PGE2-neutralizing antibody and celecoxib drug-mediated blockade of PGE2 signalling. In vivo administration of the cyclooxygenase-2 (COX2) inhibitor celecoxib effectively abolishes a PGE2- and COX2-mediated wound response gene signature, and attenuates progressive manifestation of chemoresistance in xenograft tumours, including primary xenografts derived from a patient who was resistant to chemotherapy. Collectively, these findings uncover a new underlying mechanism that models the progressive development of clinical chemoresistance, and implicate an adjunctive therapy to enhance chemotherapeutic response of bladder urothelial carcinomas by abrogating early tumour repopulation.
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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.