Experimental Neurology Unit, School of Medicine and Surgery, University of Milano Bicocca, via Cadore 48, Monza, Italy.
Milan Center for Neuroscience, University of Milano Bicocca, Piazza Ateneo Nuovo 1, Milano, Italy.
Neurotherapeutics. 2021 Oct;18(4):2324-2336. doi: 10.1007/s13311-021-01127-1. Epub 2021 Oct 19.
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.
化疗引起的周围神经毒性(CIPN)是抗肿瘤治疗,尤其是肺癌、乳腺癌、前列腺癌、胃肠道癌和生殖细胞癌,以及不同形式的白血病、淋巴瘤和多发性骨髓瘤的最常见的副作用之一。目前,没有有效的治疗方法可以预防 CIPN,而对症治疗往往无效;因此,有几个临床试验正在针对这一未满足的临床需求展开。在 CIPN 的可能药物治疗中,内源性大麻素系统的调节可能特别有前途,尤其是在那些镇痛和神经炎症调节可能有益的 CIPN 类型中。事实上,有几个临床试验正在进行,目的是更好地研究系统性化疗引起的内源性大麻素水平的变化,以及内源性大麻素系统调节在缓解 CIPN 症状方面的可能作用,这一假说得到了临床前证据的支持,但在患者中从未得到一致证实。有趣的是,内源性大麻素系统的调节可能是运动和物理疗法在 CIPN 患者中报告的疗效的基础机制之一。在这篇综述中,我们将讨论这种可能的良性相互作用。