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Nat Rev Neurol. 2017 Aug;13(8):492-504. doi: 10.1038/nrneurol.2017.88. Epub 2017 Jun 30.

Chemotherapy-induced peripheral neurotoxicity: management informed by pharmacogenetics.

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Department of Neurology, Saint Andrew's State General Hospital of Patras, Tsertidou 1 Street, 26335, Patras, Greece.
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, 08908 Hospitalet de Llobregat, Barcelona, Spain.
Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red (CIBERNED), 09193 Avinguda de Can Domènech, Bellaterra, Spain.
Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Via Bovio 6, 28100, Novara, Italy.
Experimental Neurology Unit, School of Medicine and Surgery and Milan Centre for Neuroscience, School of Medicine - University of Milano-Bicocca, via Cadore 48, 20900, Monza (MB), Italy.


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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