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Background and Aims The expanding use of chemotherapy in curative cancer treatment has simultaneously resulted in a substantial and growing cohort of cancer survivors with prolonged disability from chemotherapy‐induced peripheral neuropathy (CIPN). CIPN is associated with several commonly prescribed chemotherapeutics, including taxanes, platinum‐based drugs, vinca alkaloids, bortezomib and thalidomide. These distinct classes of chemotherapeutics, with their varied neurotoxic mechanisms, often cause patients to suffer from a broad profile of neuropathic symptoms including chronic numbness, paraesthesia, loss of proprioception or vibration sensation and neuropathic pain. Decades of investigation by numerous research groups have provided substantial insights describing this disease. Despite these advances, there is currently no effective curative or preventative treatment option for CIPN and only the dual serotonin–norepinephrine reuptake inhibitor Duloxetine is recommended by clinical guidelines for the symptomatic treatment of painful CIPN. Methods In this review, we examine current preclinical models, with our analysis focused on translational relevance and value. Results Animal models have been pivotal in achieving a better understanding of the pathogenesis of CIPN. However, it has been challenging for researchers to develop appropriate preclinical models that are effective vehicles for the discovery of translatable treatment options. Interpretation Further development of preclinical models targeting translational relevance will promote value for preclinical outcomes in CIPN studies.

Introduction/Aims Clinically, the chemotherapeutic agent oxaliplatin can cause peripheral neuropathy, impaired balance, and muscle wastage. Using a preclinical model, we investigated whether exercise intervention could improve these adverse conditions. Methods Mice were chronically treated with oxaliplatin alone or in conjunction with exercise. Behavioral studies, including mechanical allodynia, rotarod, open‐field, and grip‐strength tests, were performed. After euthanasia, multiple organs and four different muscle types were dissected and weighed. The cross‐sectional area (CSA) of muscle fibers in the gastrocnemius muscle was assessed and gene expression analysis performed on the forelimb triceps muscle. Results Oxaliplatin‐treated mice displayed reduced weight gain, mechanical allodynia, and exploratory behavior deficits that were not significantly improved by exercise. Oxaliplatin‐treated exercised mice showed modest evidence of reduced muscle wastage compared with mice treated with oxaliplatin alone, and exercised mice demonstrated evidence of a mild increase in CSA of muscle fibers. Discussion Exercise intervention did not improve signs of peripheral neuropathy but moderately reduced the negative impact of oxaliplatin chemotherapy related to muscle morphology, suggesting the potential for exploring the impact of exercise on reducing oxaliplatin‐induced neuromuscular toxicity in cancer patients.

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