Abstract

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review.

Highlights

  • Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of the pharmacological treatment of solid and hematological tumors [1]

  • Adult Wistar rats were treated with bortezomib (0.2 mg/kg i.v., 3 times/week for 8 weeks), a schedule that has been extensively investigated and it is known to induce the onset of peripheral neuropathy that reliably mimics the clinical features observed in patients receiving this drug to treat multiple myeloma [46]

  • The densitometry analysis performed on the spinal cord dorsal horn (SCDH) showed a mild albeit significant increase in CB1R immunoreactivity in bortezomib-treated rats vs controls (Fig. 4d), while no significant difference was found for CB2R (Fig. 4e)

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Summary

Introduction

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of the pharmacological treatment of solid and hematological tumors [1]. Cannabinoids for taxane induced peripheral neuropathy (trial planned to be completed in February 2022) Patients are eligible if they developed following paclitaxel- or docetaxel-based chemotherapy for breast cancer

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