ArticleOncogene2008
Hsp90 inhibition has opposing effects on wild-type and mutant p53 and induces p21 expression and cytotoxicity irrespective of p53/ATM status in chronic lymphocytic leukaemia cells.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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.
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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
44 citing papers in PubMed, 78 citations in OpenAlex.
- High-throughput drug screening identifies EGFR/MAPK pathway targeting sensitivities in organoid models of ovarian carcinosarcoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Natural products that target p53 for cancer therapy.Journal of natural medicines · 2025Review
- Review
- Therapeutic Advances and Challenges for the Management of HPV-Associated Oropharyngeal Cancer.International journal of molecular sciences · 2024Review
- P53 together with ferroptosis: a promising strategy leaving cancer cells without escape.Acta biochimica et biophysica Sinica · 2024Article
- The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023Review
- HSP90 Inhibitor PU-H71 in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia.Current issues in molecular biology · 2023Article
- Article
- BAG2 drives chemoresistance of breast cancer by exacerbating mutant p53 aggregate.Theranostics · 2023Article
- miR-550a-3p is a prognostic biomarker and exerts tumor-suppressive functions by targeting HSP90AA1 in diffuse malignant peritoneal mesothelioma.Cancer gene therapy · 2022Article
- Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer.Biomolecules · 2022Review
- Hyperthermia combined with immune checkpoint inhibitor therapy in the treatment of primary and metastatic tumors.Frontiers in immunology · 2022Review
- Targeting mutant p53 for cancer therapy: direct and indirect strategies.Journal of hematology & oncology · 2021Review
- Review
- Refractory alveolar rhabdomyosarcoma in an 11-year-old male.Cold Spring Harbor molecular case studies · 2021Article
- Recent Progress in the Synergistic Combination of Nanoparticle-Mediated Hyperthermia and Immunotherapy for Treatment of Cancer.Advanced healthcare materials · 2021Review
- Characterization of a TP53 Somatic Variant of Unknown Function From an Ovarian Cancer Patient Using Organoid Culture and Computational Modeling.Clinical obstetrics and gynecology · 2020Article
- Article
- Regulators of Oncogenic Mutant TP53 Gain of Function.Cancers · 2018Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In chronic lymphocytic leukaemia (CLL), mutation/deletion of TP53 is strongly associated with early disease progression, resistance to chemotherapy and short patient survival. Consequently, there is a pressing need to develop novel treatment protocols for this high-risk patient group. The present study was performed to evaluate Hsp90 inhibition as a possible therapeutic approach for such patients. Primary CLL cells of defined ataxia telangiectasia mutated (ATM)/p53 status were incubated with the Hsp90 inhibitor geldanamycin (GA) and analysed by western blotting for the expression of p53, p21, MDM2 and Akt. GA downregulated overexpressed mutant p53 protein (an oncogene) and upregulated wild-type (wt) p53 (a tumour suppressor). The upregulation of wt p53 by GA was independent of ATM and was accompanied by downregulation of Akt and the active form of MDM2, indicating a possible mechanism. GA also produced a p53/ATM-independent increase in the levels of p21-a potent inducer of cell-cycle arrest. In-vitro cytotoxicity studies showed that GA killed cultured CLL cells in a dose- and time-dependent fashion irrespective of their p53/ATM status and more effectively than normal blood mononuclear cells. In summary, our findings reveal important consequences of inhibiting Hsp90 in CLL cells and strongly support the therapeutic evaluation of Hsp90 inhibitors in poor-prognosis patients with p53 defects.
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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.