Translational gap in ongoing clinical trials for glioma

Abstract

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 The aim of this study was to re-evaluate this finding with a new series of 100 ongoing, but still unpublished, P2CT in order to determine if there is a TG reduction.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.

Keywords: Blood brain barrier; Brain cancer; Cancer stem cells; Clinical trial; Gliomas; Translational gap.