PDF(Pubmed)
Abstract：
Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer.
摘要：
药物再利用，将现有药物重塑为新的治疗适应症，通过跳过临床前，被认为是快速且具有成本效益的药物发现过程的有益方法，第一阶段试验和药代动力学研究。几种精神药物，包括选择性5-羟色胺再摄取抑制剂（SSRIs）和三环抗抑郁药（TCA），研究了它们在不同疾病中的潜在应用，特别是在癌症治疗中。氟西汀（FLX）是SSRIs类中处方最多的精神药物之一，用于治疗几种神经精神疾病，具有良好的安全性。FLX通过与其主要血清素能活性不同的机制表现出不同的溶瘤作用。利用其快速穿透血脑屏障的能力，FLX在脑肿瘤中特别有用。这通过使用FLX作为单一疗法或与替莫唑胺(TMZ)或放射疗法组合的不同体外和体内实验得到证明。在这篇文献综述中，我们总结了FLX对不同癌症的潜在多效性溶瘤作用，强调FLX的多方面活性及其通过多种分子机制中断癌症增殖的能力，甚至克服多药耐药（MDR）。我们阐述了成功的协同组合，如FXR/替莫唑胺和FXR/雷洛昔芬用于治疗胶质母细胞瘤和乳腺癌，分别。我们展示了将FLX装载到载体上的有益药物试验，以增强其对癌细胞的安全性和有效性。这是第一篇综述文章，广泛总结了所有以前的FLX再利用研究来治疗癌症。
