Potential use of edaravone to reduce specific side effects of chemo-, radio- and immuno-therapy of cancers
Potential use of edaravone to reduce specific side effects of chemo-, radio- and immuno-therapy of cancers
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DOI：
10.1016/j.intimp.2019.105967
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发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Bailly, Christian
中科院分区：
文献类型：
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作者：
Bailly, Christian
药物依达拉奉(EDA)用于治疗肌萎缩侧索硬化症患者或急性脑梗塞后的患者。这种合成的吡唑酮衍生物是氧自由基的有效清除剂，也是转录因子的调节剂，抑制核因子kappaB并激活Nrf2，以调节氧化应激。EDA具有抗氧化和抗炎互补的作用。这种可注射的小分子目前正被研究用于治疗几种非神经系统疾病。本文综述了EDA在肿瘤学中的潜在应用。EDA是一种温和的抗增殖剂，但已被发现在结肠癌模型中显著增强伊立替康的抗癌和抗转移活性。EDA的抗癌衍生物已被设计出来，但它们通常表现出有限的抗增殖活性。EDA的抗氧化和抗炎活性可以最好地利用来保护非肿瘤细胞免受化疗药物和辐射的损害。值得注意的是，EDA可以减轻顺铂所致的肾功能障碍、环磷酰胺的神经毒性和阿霉素的心脏毒性。经EDA治疗后，鼻咽癌患者放疗后的神经症状明显改善。该药物可用于限制辐射引起的脑损伤或口腔粘膜炎。EDA被发现可以改善自身免疫性甲状腺炎(桥本甲状腺炎)，这是使用针对免疫检查点PD-1的单抗治疗癌症患者后观察到的一种常见副作用。因此，EDA也可能有助于减少免疫治疗的特定副作用。总而言之，这些信息表明，EDA的医疗用途可能会扩展到癌症相关的疾病。EDA是一种在治疗与大脑相关的人类疾病18年后被证明是安全的药物。
The drug edaravone (EDA) is prescribed for the treatment of patients with amyotrophic lateral sclerosis or after an acute cerebral infarction. This synthetic pyrazolone derivative is a potent scavenger of oxygen free radicals and also functions as a modulator of transcription factors, repressing NF kappa B and activating Nrf2, to regulate oxidative stress. EDA displays complementary anti-oxidative and anti-inflammatory effects. The injectable small molecule is currently investigated for the treatment of several non-neurological diseases. The potential interest of EDA in oncology is reviewed here. EDA is a mild antiproliferative agent but has been found to enhance significantly the anticancer and antimetastatic activities of irinotecan in a colon cancer model. Anticancer derivatives of EDA have been designed but they generally display a limited antiproliferative activity. The antioxidant and anti-inflammatory activity of EDA can be best exploited to protect non-tumor cells from damages induced by chemotherapeutic drugs and radiations. Notably EDA can reduce the renal dysfunction induced by cisplatin, the neurotoxicity of cyclophosphamide and the cardiotoxicity of doxorubicin. Upon treatment with EDA, a significant improvement in neurologic symptoms has been observed in patients with nasopharyngeal carcinoma after radiotherapy. The drug could be used to limit radiation-induced brain injury or oral mucositis. EDA was found to ameliorate autoimmune thyroiditis (Hashimoto thyroiditis), which is a frequent side effect observed after treatment of cancer patients with monoclonal antibodies targeting the immune checkpoint PD-1. Therefore, EDA could also be useful to reduce specific side effects of immuno-therapy. Collectively, the information suggests that the medical use of EDA, a drug with a proven safety after 18 years of use in brain-related Human diseases, could be extended to cancer-related conditions.