Lui Austin, Vanleuven Jordan, Perekopskiy David, Liu Dewey, Xu Desiree, Alzayat Omar, Elgokhy Taiseer, Do Timothy, Gann Meghan, Martin Ryan, Liu Da-Zhi
Department of Neurology, University of California at Davis, Davis, CA 95618, USA.
Department of Neurological Surgery and Neurology, University of California at Davis, Davis, CA 95618, USA.
Pharmaceuticals (Basel). 2022 Dec 13;15(12):1546. doi: 10.3390/ph15121546.
Cancers and neurological disorders are two major types of diseases. We previously developed a new concept termed "Aberrant Cell Cycle Diseases" (ACCD), revealing that these two diseases share a common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncogene activation and tumor suppressor inactivation, which are hallmarks of tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase inhibition, tumor suppressor elevation) can be leveraged for neurological treatments. The United States Food and Drug Administration (US FDA) has so far approved 74 kinase inhibitors, with numerous other kinase inhibitors in clinical trials, mostly for the treatment of cancers. In contrast, there are dire unmet needs of FDA-approved drugs for neurological treatments, such as Alzheimer's disease (AD), intracerebral hemorrhage (ICH), ischemic stroke (IS), traumatic brain injury (TBI), and others. In this review, we list these 74 FDA-approved kinase-targeted drugs and identify those that have been reported in preclinical and/or clinical trials for neurological disorders, with a purpose of discussing the feasibility and applicability of leveraging these cancer drugs (FDA-approved kinase inhibitors) for neurological treatments.
癌症和神经疾病是两大类疾病。我们之前提出了一个新的概念，称为“异常细胞周期疾病”（ACCD），揭示了这两种疾病具有异常细胞周期重新进入的共同机制。异常细胞周期重新进入表现为激酶/癌基因激活和肿瘤抑制因子失活，这是癌症中肿瘤生长和神经疾病中神经元死亡的标志。因此，一些癌症治疗方法（如激酶抑制、肿瘤抑制因子提升）可用于神经疾病治疗。美国食品药品监督管理局（US FDA）迄今已批准了74种激酶抑制剂，还有许多其他激酶抑制剂正在进行临床试验，主要用于癌症治疗。相比之下，对于神经疾病治疗，如阿尔茨海默病（AD）、脑出血（ICH）、缺血性中风（IS）、创伤性脑损伤（TBI）等，FDA批准的药物存在迫切未满足的需求。在本综述中，我们列出了这74种FDA批准的激酶靶向药物，并确定了那些已在神经疾病的临床前和/或临床试验中报道的药物，目的是讨论利用这些癌症药物（FDA批准的激酶抑制剂）进行神经疾病治疗的可行性和适用性。
