Targeting strategies for oxaliplatin-induced peripheral neuropathy: clinical syndrome, molecular basis, and drug development

Abstract

Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN) is a severe clinical problem and potentially permanent side effect of cancer treatment. For the management of OIPN, accurate diagnosis and understanding of significant risk factors including genetic vulnerability are essential to improve knowledge regarding the prevalence and incidence of OIPN as well as enhance strategies for the prevention and treatment of OIPN. The molecular mechanisms underlying OIPN are complex, with multi-targets and various cells causing neuropathy. Furthermore, mechanisms of OIPN can reinforce each other, and combination therapies may be required for effective management. However, despite intense investigation in preclinical and clinical studies, no preventive therapies have shown significant clinical efficacy, and the established treatment for painful OIPN is limited. Duloxetine is the only agent currently recommended by the American Society of Clinical Oncology. The present article summarizes the most recent advances in the field of studies on OIPN, the overview of the clinical syndrome, molecular basis, therapy development, and outlook of future drug candidates. Importantly, closer links between clinical pain management teams and oncology will advance the effectiveness of OIPN treatment, and the continued close collaboration between preclinical and clinical research will facilitate the development of novel prevention and treatments for OIPN.

Enzyme-Catalyzed Synthesis of Selenium-Doped Manganese Phosphate for Synergistic Therapy of Drug-Resisted Colorectal Tumor

“…As a bifunctional alkylating agent, OX could interfere with DNA replication and ultimately induce apoptosis of tumor cells [41][42][43]. Despite oxaliplatin-based chemotherapy being successfully applied for colorectal cancer therapy, OX could lead to serious side effects, such as neurotoxicity due to non-speci c uptake [44][45][46]. Moreover, it is less effective for tumor cells with MDR.…”

Revisiting the Anti-cancer Toxicity of Clinically Approved Platinating Derivatives

“…As with CDDP and CP, OXP has limitations to its use, either because of side effects, hypersensitivity, or chemoresistance. The major dose-limiting side effect of OXP is peripheral neurotoxicity, occurring acutely or chronically [252,260,[289][290][291]. Acute OXP-induced peripheral neuropathy (OIPN) occurs in the majority of patients and can be exacerbated by cold stimulation; the symptoms begin to present within hours of the infusion and can last up to 7 days [252,291].…”

Antioxidant and Neuroprotective Effect of a Grape Pomace Extract on Oxaliplatin-Induced Peripheral Neuropathy in Rats: Biochemical, Behavioral and Histopathological Evaluation

“…Up until now, several researchers have reported that severe damage in Dorsal Root Ganglion (DRG) neurons leads to the development of PN [ 17 , 18 , 19 , 20 ]. In particular, it was found that oxaliplatin causes the selective atrophy of a subpopulation of dorsal root ganglion neurons, large DRG neurons (≥1000 μm 2 ), without interfering with total DRG neuronal cell number [ 21 ].…”