Sigma-1 receptor : a new player in neuroprotection against chemotherapy-induced peripheral neuropathy
Bruna, Jordi (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Velasco, Roser (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Date:	2018
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra, i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Oxaliplatin ; Chemotherapy-induced peripheral neuropathy ; Sigma-1 receptor ; Neurotoxicity ; MR309 ; E-52862
Published in:	Neural Regeneration Research, Vol. 13 (may 2018) , p. 775-778, ISSN 1876-7958

DOI: 10.4103/1673-5374.232459
PMID: 29862996

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