Drug Repositioning for the Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy: A Mechanism- and Screening-Based Strategy.

Shota Yamamoto,Nobuaki Egashira

doi:10.3389/fphar.2020.607780

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse effect observed in most patients treated with neurotoxic anti-cancer drugs. Currently, there are no therapeutic options available for the prevention of CIPN. Furthermore, few drugs are recommended for the treatment of existing neuropathies because the mechanisms of CIPN remain unclear. Each chemotherapeutic drug induces neuropathy by distinct mechanisms, and thus we need to understand the characteristics of CIPN specific to individual drugs. Here, we review the known pathogenic mechanisms of oxaliplatin- and paclitaxel-induced CIPN, highlighting recent findings. Cancer chemotherapy is performed in a planned manner; therefore, preventive strategies can be planned for CIPN. Drug repositioning studies, which identify the unexpected actions of already approved drugs, have increased in recent years. We have also focused on drug repositioning studies, especially for prevention, because they should be rapidly translated to patients suffering from CIPN.

Highlights

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting adverse effect of neurotoxic chemotherapeutic agents
Articles related to CIPN pathology and drug repositioning studies for the prevention and/ or treatment of CIPN using cellular models or animal models were manually selected based on originality and relevance to the scope of this review
Oxaliplatin is highly effective for the treatment of cancers, it often causes severe neuropathic symptoms that can be divided into two types: acute-onset cold hypersensitivity within a few days after treatment and chronic sensory neuropathy including tactile allodynia and numbness occurring after repeated treatments

Summary

INTRODUCTION

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting adverse effect of neurotoxic chemotherapeutic agents. There are many clinical trials investigating the effectiveness of approved drugs against CIPN (Brewer et al, 2016; Cavaletti and Marmiroli, 2020). Most of these available drugs were shown to have poor efficacy, except for duloxetine, which is moderately recommended for the treatment of existing CIPN (Hershman et al, 2014; Loprinzi et al, 2020). Drug repositioning studies attempt to identify unexpected actions with approved drugs used in clinical practice This approach can reduce the duration and cost of drug development because the pharmacokinetics and safety of approved drugs have already been examined in humans. Detailed information about the developmental mechanisms or clinical aspects of CIPN has been reported in previous excellent reviews (Cavaletti and Marmiroli, 2010; Hershman et al, 2014; Sisignano et al, 2014; Loprinzi et al, 2020)

METHODOLOGY

CONCLUSIONS