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  • Review Article
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Chemotherapy-induced peripheral neurotoxicity: management informed by pharmacogenetics

Nature Reviews Neurology volume 13, pages 492–504 (2017)Cite this article

Subjects

Key Points

  • Peripheral neurotoxicity is potentially permanent and ranks among the most common non-haematological adverse effects of chemotherapy

  • Identifying patients at high risk of chemotherapy-induced peripheral neurotoxicity (CIPN) is paramount

  • The identification of a clinical or genetic profile that can detect patients at high risk of CIPN still represents an unmet need

  • The methodology of pharmacogenetic studies on CIPN could be improved

  • Further studies are warranted to identify genetic associations that could inform the management of patients with CIPN

Abstract

The increasing availability of sophisticated methods to characterize human genetic variation has enabled pharmacogenetic data to be used not only to predict responses to treatment (in the context of so-called personalized medicine), but also to identify patients at high or low risk of specific treatment-related adverse effects. Over the past two decades, extensive attempts have been made to understand the genetic basis of chemotherapy-induced peripheral neurotoxicity (CIPN), one of the most severe non-haematological adverse effects of cancer treatment. Despite substantial efforts, however, the identification of a genetic profile that can detect patients at high risk of CIPN still represents an unmet need, as the information obtained from pharmacogenetic studies published so far is inconsistent at best. Among the reasons for these inconsistencies, methodological flaws and the poor reliability of existing tools for assessing CIPN features and severity are particularly relevant. This Review provides a critical update of the pharmacogenetics of CIPN, focusing on the studies published since 2011. Strategies for improving the reliability of future pharmacogenetic studies of CIPN are also discussed.

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Figure 1: A large number of genes are potentially associated with CIPN.
Figure 2: Cellular pathways implicated in CIPN.
Figure 3: Common problems with the interpretation of pharmacogenetic studies in CIPN.

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Acknowledgements

The authors' research work was supported by grant 2013–0842 from Fondazione Cariplo (to A.A.G. and G.C.), by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC) Progetto IG 2016 Id.18631 (to G.C.) and partially by grant PI1501303 from Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional (FEDER) to J.B.

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Authors and Affiliations

  1. Department of Neurology, Saint Andrew's State General Hospital of Patras, Tsertidou 1 Street, Patras, 26335, Greece

    Andreas A. Argyriou

  2. Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO l'Hospitalet, Bellvitge Institute for Biomedical Research (IDIBELL), Hospital Duran i Reynals, 3a planta, Gran Via de l'Hospitalet 199, Hospitalet de Llobregat, Barcelona, 08908, Spain

    Jordi Bruna

  3. Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red (CIBERNED), Avinguda de Can Domènech, Bellaterra, 09193, Spain

    Jordi Bruna

  4. Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Via Bovio 6, Novara, 28100, Italy

    Armando A. Genazzani

  5. Experimental Neurology Unit, School of Medicine and Surgery and Milan Centre for Neuroscience, School of Medicine — University of Milano-Bicocca, via Cadore 48, Monza (MB), 20900, Italy

    Guido Cavaletti

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Each author contributed to all aspects of the preparation of this Review (researching data for the article, writing the manuscript, discussions of content and review or editing of the article before submission).

Corresponding author

Correspondence to Andreas A. Argyriou.

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Supplementary information

Supplementary information S1 (table)

Pharmacogenetic studies related to chemotherapy-induced peripheral neurotoxicity (CIPN) in patients treated with platinum compounds. (DOC 52 kb)

Supplementary information S2 (table)

Pharmacogenetic studies related to chemotherapy-induced peripheral neurotoxicity (CIPN) in patients treated with bortezomib. (DOC 50 kb)

Supplementary information S3 (table)

Pharmacogenetic studies related to chemotherapy-induced peripheral neurotoxicity (CIPN) in patients treated with taxanes. (DOC 51 kb)

Supplementary information S4 (table)

Pharmacogenetic studies related to chemotherapy-induced peripheral neurotoxicity (CIPN) in patients treated with thalidomide or vincristine. (DOC 49 kb)

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Argyriou, A., Bruna, J., Genazzani, A. et al. Chemotherapy-induced peripheral neurotoxicity: management informed by pharmacogenetics. Nat Rev Neurol 13, 492–504 (2017). https://doi.org/10.1038/nrneurol.2017.88

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