Department of Neurosurgery, Institute of Nervous System Diseases, The Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou, 221002, China.
Department of Psychiatry, The Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University, 379 Tong-Shan Road, Xuzhou, 221004, China.
Cancer Lett. 2022 Feb 28;527:140-149. doi: 10.1016/j.canlet.2021.12.014. Epub 2021 Dec 16.
Psychotropic drugs can penetrate the blood-brain barrier and regulate the levels of neurotransmitters and neuromodulators such as γ-aminobutyric acid, glutamate, serotonin, dopamine, and norepinephrine in the brain, and thus influence neuronal activity. Neuronal activity in the tumor microenvironment can promote the growth and expansion of glioma. There is increasing evidence that in addition to their use in the treatment of mental disorders, antipsychotic, antidepressant, and mood-stabilizing drugs have clinical potential for cancer therapy. These drugs have been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. In this review, we summarize findings from preclinical and clinical studies investigating the use of antipsychotics, antidepressants, and mood stabilizers in the treatment of various types of cancer, with a focus on glioma; and discuss their presumed antitumor mechanisms. The existing evidence indicates that psychotropic drugs with established pharmacologic and safety profiles can be repurposed as anticancer agents, thus providing new options for the treatment of glioma.
精神药物可以穿透血脑屏障,调节大脑中神经递质和神经调质的水平,如γ-氨基丁酸、谷氨酸、血清素、多巴胺和去甲肾上腺素,从而影响神经元活动。肿瘤微环境中的神经元活动可以促进神经胶质瘤的生长和扩张。越来越多的证据表明,除了在精神障碍治疗中的应用外,抗精神病药、抗抑郁药和情绪稳定剂在癌症治疗方面也具有临床潜力。这些药物已被证明通过针对与细胞增殖、凋亡或侵袭/迁移相关的信号通路,或通过增加神经胶质瘤细胞对常规化疗或放疗的敏感性,来抑制神经胶质瘤的恶性进展。在这篇综述中,我们总结了关于抗精神病药、抗抑郁药和情绪稳定剂在治疗各种类型癌症(重点是神经胶质瘤)中的应用的临床前和临床研究结果,并讨论了它们的抗肿瘤机制。现有证据表明,具有既定药理学和安全性特征的精神药物可以被重新用于癌症治疗,从而为神经胶质瘤的治疗提供了新的选择。