Guishard Alecia Florence, Yakisich Juan Sebastian, Azad Neelam, Iyer Anand Krishnan V
Governor's School for Science & Technology, Hampton University, VA 23668, USA.
School of Pharmacy, Department of Pharmaceutical Sciences, Hampton University, VA 23668, USA.
J Clin Neurosci. 2018 Jan;47:28-42. doi: 10.1016/j.jocn.2017.10.001. Epub 2017 Oct 21.
Despite the vast amounts of information gathered about gliomas, the overall survival of glioma patients has not improved in the last four decades. This could partially be due to an apparent failure to include basic concepts of glioma biology into clinical trials. Specifically, attempts to overcome the limitations of the blood brain barrier (BBB) and the chemoresistance of glioma stem cells (GSCs) were seldom included (a phenomenon known as the translational gap, TG) in a study involving 29 Phase I/II clinical trials (P2CT) published in 2011. The aim of this study was to re-evaluate this finding with a new series of 100 ongoing, but still unpublished, P2CT in order to determine if there is a TG reduction. As indicators, we evaluated in each P2CT the number of drugs tested, concomitant radiotherapy, and the ability of drugs to pass the BBB and to target GSCs. Compared to clinical trials published in 2011, we found that while in OCT there is an increase in the number of P2CT using two drugs (from 24.1% to 44.9%), and an increase in the number of drugs able to pass the BBB (7.14% versus 64.29%) and target GSCs (0% versus 16.3%), there was a decrease in the number of P2CT using concomitant radiotherapy (34.5% versus 18.37%). Overall our results suggest that there is only a modest improvement regarding reducing the TG because the vast majority of ongoing P2CT are still not including well known concepts of glioma biology important for a successful treatment.
尽管已经收集了大量关于胶质瘤的信息，但在过去四十年中，胶质瘤患者的总体生存率并未得到改善。这可能部分归因于在临床试验中明显未能纳入胶质瘤生物学的基本概念。具体而言，在2011年发表的一项涉及29项I/II期临床试验（P2CT）的研究中，很少有克服血脑屏障（BBB）限制和胶质瘤干细胞（GSCs）化疗耐药性的尝试（一种被称为转化差距，TG的现象）。本研究的目的是用一系列新的100项正在进行但仍未发表的P2CT重新评估这一发现，以确定是否存在TG减少的情况。作为指标，我们在每项P2CT中评估了测试药物的数量、同步放疗情况，以及药物通过BBB和靶向GSCs的能力。与2011年发表的临床试验相比，我们发现，虽然在正在进行的试验中，使用两种药物的P2CT数量有所增加（从24.1%增至44.9%），能够通过BBB的药物数量增加（7.14%对64.29%）以及靶向GSCs的药物数量增加（0%对16.3%），但使用同步放疗的P2CT数量有所减少（34.5%对18.37%）。总体而言，我们的结果表明，在减少TG方面只有适度改善，因为绝大多数正在进行的P2CT仍然没有纳入对成功治疗至关重要的胶质瘤生物学的知名概念。
