ArticleBritish journal of cancer2011
Targeted inhibition of mitochondrial Hsp90 suppresses localised and metastatic prostate cancer growth in a genetic mouse model of disease.
Article in British journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Membrane-associated HDAC11: A potential new therapeutic targeting compartment in cancer cells.Biochemistry and biophysics reports · 2026Article
- Cancer-associated mitochondrial homeostasis disrupted and retrograde signaling activated.Medical oncology (Northwood, London, England) · 2026Review
- Hypoxia-ROS-HSP Triad Axis in Cancer: Mechanisms, Crosstalk, and Therapeutic Implications.Cells · 2026Review
- Current therapeutic interventions to target cancer stem cells for metastasis.International journal of clinical oncology · 2026Review
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- PKR Mediates the Mitochondrial Unfolded Protein Response through Double-Stranded RNA Accumulation under Mitochondrial Stress.International journal of molecular sciences · 2024Article
- Succinate-Directed Approaches for Warburg Effect-Targeted Cancer Management, an Alternative to Current Treatments?Cancers · 2023Review
- The development of cancers research based on mitochondrial heat shock protein 90.Frontiers in oncology · 2023Review
- Feasibility and safety of targeting mitochondria for cancer therapy - preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor.Cancer biology & therapy · 2022Article
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- TRAP1 Chaperones the Metabolic Switch in Cancer.Biomolecules · 2022Review
- Antitumor Activity of a Mitochondrial-Targeted HSP90 Inhibitor in Gliomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Failure to Guard: Mitochondrial Protein Quality Control in Cancer.International journal of molecular sciences · 2021Review
- A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation.G3 (Bethesda, Md.) · 2020Article
- The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy.Frontiers in oncology · 2020Review
- Targeting STAT3 and oxidative phosphorylation in oncogene-addicted tumors.Redox biology · 2019Review
- Mitochondrial Involvement in Migration, Invasion and Metastasis.Frontiers in cell and developmental biology · 2019Review
- Mitochondria in cancer metabolism, an organelle whose time has come?Biochimica et biophysica acta. Reviews on cancer · 2018Review
- Mitochondrial HSP90 Accumulation Promotes Vascular Remodeling in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2018Article
- Profiles of Radioresistance Mechanisms in Prostate Cancer.Critical reviews in oncogenesis · 2018Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe molecular chaperone heat shock protein-90 (Hsp90) is a promising cancer drug target, but current Hsp90-based therapy has so far shown limited activity in the clinic.
methodsWe tested the efficacy of a novel mitochondrial-targeted, small-molecule Hsp90 inhibitor, Gamitrinib (GA mitochondrial matrix inhibitor), in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The TRAMP mice receiving 3-week or 5-week systemic treatment with Gamitrinib were evaluated for localised or metastatic prostate cancer, prostatic intraepithelial neoplasia (PIN) or localised inflammation using magnetic resonance imaging, histology and immunohistochemistry. Treatment safety was assessed histologically in organs collected at the end of treatment. The effect of Gamitrinib on mitochondrial dysfunction was studied in RM1 cells isolated from TRAMP tumours.
resultsSystemic administration of Gamitrinib to TRAMP mice inhibited the formation of localised prostate tumours of neuroendocrine or adenocarcinoma origin, as well as metastatic prostate cancer to abdominal lymph nodes and liver. The Gamitrinib treatment had no effect on PIN or prostatic inflammation, and caused no significant animal weight loss or organ toxicity. Mechanistically, Gamitrinib triggered acute mitochondrial dysfunction in RM1 cells, with loss of organelle inner membrane potential and release of cytochrome-c in the cytosol.
conclusionsThe Gamitrinib has pre-clinical activity and favourable tolerability in a genetic model of localised and metastatic prostate cancer in immunocompetent mice. Selective targeting of mitochondrial Hsp90 could provide novel molecular therapy for patients with advanced prostate cancer.
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