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Bortezomib-induced peripheral neurotoxicity: an update

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Abstract

This review paper provides a critical exploration of updates concerning the spectrum of characteristics and treatment options of bortezomib-induced peripheral neuropathy (BIPN). Emphasis is given on pathogenesis issues. Although the mechanism underlying BIPN still remains elusive, it is increasingly acknowledged that the inhibition of proteasome activity in dorsal root ganglia and peripheral nerves, the mitochondrial-mediated disruption of Ca++ intracellular homeostasis and the disregulation in nuclear factor κB and brain-derived neurotrophic factor play a significant pathogenic role. Assessment of BIPN is based on comprehensive grading scales, using a combination of “subjective” and “objective” parameters, which turn out to be ambiguously interpreted, thus leading to both under- and misreporting of its true incidence and severity. BIPN is clinically defined as a typical example of a dose-dependent, distally attenuated painful, sensory neuronopathy. Patients pre-treated with neurotoxic regimens and those with pre-existing neuropathy are more likely to develop severe neurotoxicity. To date, there is no effective pharmacological treatment to prevent BIPN, and therefore, interventions remain merely symptomatic to focus on the alleviation of neuropathic pain. Hence, strict adherence to the dose reduction and schedule change algorithm is recommended in order to prevent treatment-emergent BIPN and allow the continuation of treatment. Further studies in animal models and humans, including experimental, clinical, neurophysiological and pharmacogenetic approaches, are needed to allow the identification of the true spectrum of BIPN pathogenesis and characteristics. It is expected that such comprehensive approaches would be the starting point for the development of early preventive and therapeutic interventions against BIPN.

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Acknowledgments

Each author jointly contributed to the preparation of this review paper.

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We have no conflicts of interest. No funding source played a role in the preparation of this paper or in the decision to submit it for publication.

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Authors and Affiliations

  1. Department of Neurology, “Saint Andrew’s” State General Hospital of Patras, 26335, Patras, Greece

    Andreas A. Argyriou

  2. Division of Oncology, Department of Medicine, University of Patras Medical School, Rion, Patras, Greece

    Andreas A. Argyriou & Haralabos P. Kalofonos

  3. Experimental Neurology Unit, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, Italy

    Guido Cavaletti

  4. Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain

    Jordi Bruna

  5. Department of Neurology, University of Ioannina Medical School, Ioannina, Greece

    Athanasios P. Kyritsis

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  1. Andreas A. Argyriou
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Correspondence to Andreas A. Argyriou.

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Argyriou, A.A., Cavaletti, G., Bruna, J. et al. Bortezomib-induced peripheral neurotoxicity: an update. Arch Toxicol 88, 1669–1679 (2014). https://doi.org/10.1007/s00204-014-1316-5

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