Koehler Abigail, Karve Aniruddha, Desai Pankaj, Arbiser Jack, Plas David R, Qi Xiaoyang, Read Renee D, Sasaki Atsuo T, Gawali Vaibhavkumar S, Toukam Donatien K, Bhattacharya Debanjan, Kallay Laura, Pomeranz Krummel Daniel A, Sengupta Soma
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Division of Pharmaceutical Sciences, University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH 45229, USA.
Pharmaceuticals (Basel). 2021 Jan 28;14(2):99. doi: 10.3390/ph14020099.
Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor. The current standard of care for GBM is the Stupp protocol which includes surgical resection, followed by radiotherapy concomitant with the DNA alkylator temozolomide; however, survival under this treatment regimen is an abysmal 12-18 months. New and emerging treatments include the application of a physical device, non-invasive 'tumor treating fields' (TTFs), including its concomitant use with standard of care; and varied vaccines and immunotherapeutics being trialed. Some of these approaches have extended life by a few months over standard of care, but in some cases are only available for a minority of GBM patients. Extensive activity is also underway to repurpose and reposition therapeutics for GBM, either alone or in combination with the standard of care. In this review, we present select molecules that target different pathways and are at various stages of clinical translation as case studies to illustrate the rationale for their repurposing-repositioning and potential clinical use.
多形性胶质母细胞瘤(GBM)是一种高度恶性的原发性脑肿瘤。目前GBM的标准治疗方案是Stupp方案,包括手术切除,随后进行放疗并联合DNA烷化剂替莫唑胺;然而,在这种治疗方案下的生存期仅为糟糕的12 - 18个月。新出现的治疗方法包括应用一种物理设备,即非侵入性的“肿瘤治疗电场”(TTFs),包括其与标准治疗联合使用;以及正在试验的各种疫苗和免疫疗法。其中一些方法使生存期比标准治疗延长了几个月,但在某些情况下仅适用于少数GBM患者。针对GBM的治疗药物重新利用和重新定位的广泛研究也在进行中,这些药物可单独使用或与标准治疗联合使用。在本综述中,我们展示了一些针对不同途径且处于临床转化不同阶段的精选分子,作为案例研究来说明它们重新利用 - 重新定位的原理及潜在临床用途。