中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (5): 775-778.doi: 10.4103/1673-5374.232459

• 综述:周围神经损伤修复保护与再生 • 上一篇    下一篇

Sigma-1受体:对化疗致周围神经病起神经保护作用

  

  • 收稿日期:2018-03-19 出版日期:2018-05-15 发布日期:2018-05-15

Sigma-1 receptor: a new player in neuroprotection against chemotherapy-induced peripheral neuropathy

Jordi Bruna1, 2, Roser Velasco1, 2   

  1. 1 Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO L’Hospitalet, IDIBELL (Institut d’Investigació Biomèdica de Bellvitge), Barcelona,Spain
    2 Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, and Centro de Investigación Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain
  • Received:2018-03-19 Online:2018-05-15 Published:2018-05-15
  • Contact: Jordi Bruna, Ph.D., M.D.,35078jbe@comb.cat.

摘要:

orcid:0000-0001-6895-5047(Jordi Bruna)

Abstract:

 

Chemotherapy-induced peripheral neuropathy is a very frequent neurological complication in cancer. Oxaliplatin (OXA) is a platinum analogue used as a first-line agent in the treatment of colorectal cancer. OXA induced peripheral neuropathy (OIN) is the main toxicity both during and after the completion of chemotherapy that presents as two distinct syndromes: acute and chronic neuropathy. None of the neuroprotective agents previously tested had prevented or limited the acute and/or chronic OIN. MR309 (previously developed as E-52862) is a novel selective sigma-1 receptor (S1R) antagonist with preclinical analgesic activity in OXA-induced neuropathic pain in animal models. This review analyzes the results of the recently published phase II, randomized, double-blind, placebo-controlled clinical trial including 124 patients with colorectal cancer (CRC) treated with MR309. This study shows encouraging findings in the setting of neuroprotection against OIN with an acceptable safety profile. The study demonstrated MR309 usefulness in decreasing acute OIN, by reducing cold hypersensitivity experienced by patients, and pointed to the amelioration of chronic OIN by lowering the proportion of patients who developed severe chronic OIN. In addition, we provide a summary and discussion on the pathways that can be modulated by the S1R to explain the observed clinical benefits in the OIN.

Key words: oxaliplatin, chemotherapy-induced peripheral neuropathy, sigma-1 receptor, neurotoxicity, MR309, E-52862