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Reply to ‘Mitochondrial dysfunction as a crucial mediator of ADT-induced cardiovascular risk’

Nature Reviews Urology volume 22, page 564 (2025)Cite this article

We appreciate the thoughtful comments from Yu-Hsiang Lin et al. regarding our Review article (Assessing the effects of prostate cancer therapies on cardiovascular health. Nat. Rev. Urol. https://doi.org/10.1038/s41585-025-01002-0; 2025)1. In their Correspondence (Mitochondrial dysfunction as a crucial mediator of ADT-induced cardiovascular risk. Nat. Rev. Urol. https://doi.org/10.1038/s41585-025-01050-6; 2025)2, the authors highlight the potential role of mitochondrial dysfunction as a unifying mechanism underlying the diverse systemic effects of androgen deprivation therapy (ADT), including cardiovascular, metabolic and neurocognitive complications.

We agree that mitochondrial dysfunction is indeed a possible understudied contributor to ADT-induced cardiotoxicity. As Lin et al. note, low testosterone levels have been linked to oxidative stress and impaired mitochondrial function, which could contribute to conditions such as atherosclerosis, arrhythmias and heart failure3,4. These observations are further supported by preclinical and clinical evidence suggesting that ADT disrupts processes heavily reliant on mitochondrial integrity, including cellular energy metabolism, redox balance and apoptosis pathways5,6. Beyond cardiovascular effects, we also agree that mitochondrial dysfunction might potentially have a role in the progression of castration-resistant prostate cancer and ADT-associated neurocognitive decline. The observed shift towards aerobic glycolysis, often referred to as the Warburg effect, in prostate cancer cells under ADT might suggest a possible role for mitochondrial regulation in both oncogenesis and treatment resistance7.

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References

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Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Gatineau Hospital, McGill University, Gatineau, Quebec, Canada

    Steven Tisseverasinghe

  2. Department of Radiation Oncology, Dalhousie University, QEII Cancer Centre, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada

    Marwan Tolba

  3. Division of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

    Boris Bahoric

  4. Centre Hospitalier de l’Université de Montréal, Université de Montréal, Montreal, Quebec, Canada

    Fred Saad

  5. Department of Oncology, Division of Radiation Oncology, McGill University, Montreal, Quebec, Canada

    Fred Saad & Tamim Niazi

Authors
  1. Steven Tisseverasinghe
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  2. Marwan Tolba
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  3. Boris Bahoric
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  4. Fred Saad
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  5. Tamim Niazi
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Corresponding authors

Correspondence to Fred Saad or Tamim Niazi.

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Competing interests

S.T. receives honoraria and consulting fees from Tolmar, AbbVie, Knight, Bayer, Janssen and Sumitomo pharma. M.T. receives honoraria and consulting fees from AbbVie, Tersera and Knight. F.S. has grants/contracts with Janssen, Bayer, Merck, Pfizer, Astellas, BMS, Novartis, Sanofi and AstraZeneca; receives consulting fees from Janssen, Bayer, Astellas, Novartis, Sanofi, AstraZeneca, Merck, Pfizer, Somitomo and Tolmar; and receives honoraria from Janssen, Bayer, Somitomo, Astellas, Novartis, Sanofi, AstraZeneca, Merck, Pfizer and Tolmar. T.N. has grants/contracts with Bayer, Jansen, Astellas, Tersera and Sanofi Canada; receives consulting fees from AbbVie, Astellas, Jansen, Tersera, Tolmar, Bayer, AAA, Pfizer, Knight, AstraZeneca and Sumitomo pharma; receives support for attending meetings/travel from Jansen, Tolmar, Knight and Bayer; and is the chair of the Quebec GU Radiation oncology group and co-chair of the Canadian GU radiation oncology group. B.B. declares no competing interests.

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Tisseverasinghe, S., Tolba, M., Bahoric, B. et al. Reply to ‘Mitochondrial dysfunction as a crucial mediator of ADT-induced cardiovascular risk’. Nat Rev Urol 22, 564 (2025). https://doi.org/10.1038/s41585-025-01049-z

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