Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, Florida.
Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
J Histochem Cytochem. 2021 Dec;69(12):749-773. doi: 10.1369/00221554211025482. Epub 2021 Jun 24.
Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration-approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.
与其他癌症病因相比,成人脑肿瘤可能不常见,但它们仍然是最致命的肿瘤之一,生存率非常低。目前的治疗方法包括手术切除、化疗和放疗。然而,耐药率不断上升,部分原因是癌症干细胞 (CSC)。CSC 是肿瘤组织中存在的一类癌细胞亚群,具有自我更新能力,并能分化增殖为多个细胞谱系。研究这些 CSC 有助于加深对致癌作用的认识,靶向 CSC 可能克服现有的治疗耐药性。一种利用新药的方法是通过药物重用来靶向这些 CSC,药物重用来利用已经获得食品和药物管理局批准、用于一种明确疾病的药物,针对新的适应症。这种方法可以节省设计全新疗法所花费的时间和金钱。在这篇综述中,我们将举例说明已经在脑肿瘤中使用的药物重利用策略,然后进一步详细阐述这些方法,特别是那些针对驻留 CSC 的方法,如何帮助药物重利用领域达到一个新的水平。