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Targeting therapy-induced senescence as a novel strategy to combat chemotherapy-induced peripheral neuropathy

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Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting adverse effect of anticancer therapy that complicates the lifestyle of many cancer survivors. There is currently no gold-standard for the assessment or management of CIPN. Subsequently, understanding the underlying mechanisms that lead to the development of CIPN is essential for finding better pharmacological therapy. Therapy-induced senescence (TIS) is a form of senescence that is triggered in malignant and non-malignant cells in response to the exposure to chemotherapy. Recent evidence has also suggested that TIS develops in the dorsal root ganglia of rodent models of CIPN. Interestingly, several components of the senescent phenotype are commensurate with the currently established primary processes implicated in the pathogenesis of CIPN including mitochondrial dysfunction, oxidative stress, and neuroinflammation. In this article, we review the literature that supports the hypothesis that TIS could serve as a holistic mechanism leading to CIPN, and we propose the potential for investigating senotherapeutics as means to mitigate CIPN in cancer survivors.

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Funding

Dr. Tareq Saleh is supported for this work by the Deanship of Scientific Research, The Hashemite University (grant no.743/51/2022).

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Authors and Affiliations

  1. Department of Anatomy and Histology, School of Medicine, The University of Jordan, Amman, 11942, Jordan

    Mohammad Alsalem & Sarah Bloukh

  2. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    Amr Ellaithy

  3. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Amr Ellaithy

  4. Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, 21163, Jordan

    Mansour Haddad

  5. Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, 13133, Jordan

    Tareq Saleh

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Contributions

MA wrote the section on the mechanisms of CIPN. AE wrote the section on the clinical challenges associated with the treatment of CIPN. SB wrote the section on TIS. MH contributed to the writing and editing of all sections. TS wrote the section on the proposed model, designed the figure, and wrote and edited the manuscript.

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Correspondence to Tareq Saleh.

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Alsalem, M., Ellaithy, A., Bloukh, S. et al. Targeting therapy-induced senescence as a novel strategy to combat chemotherapy-induced peripheral neuropathy. Support Care Cancer 32, 85 (2024). https://doi.org/10.1007/s00520-023-08287-0

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