Identification of Inhibitors of Glioblastoma Stem Cells by High-Throughput Screening

Overview

Glioblastomas (GBM) are the most common primary malignant brain tumor in adults and are recognized as one of the deadliest forms of cancer. Despite aggressive therapy consisting of maximal surgical resection followed by concomitant radiation and temozolomide (TMZ) chemotherapy, GBM remains to have a median survival time of ~ 15 months. The presence of neoplastic cells with characteristics of neural stem cells, referred to as glioma stem cells (GSC), has been suggested to be the root cause for tumor initiation and progression. In an effort to identify agents that specifically inhibit GSC growth, a drug screen of over 3700 bioactive small molecules was recently conducted. The potency of these compounds was tested on six GBM patient derived neurosphere lines (HSR029913, HSR040622, HSR040822, CCF3691, CCF3832, and CCF08-387) at different concentrations. Next, the specificity of these compounds in killing GSCs was determined. To this end, the activities of these compounds were tested against immortalized human neural stem cells (v-Myc hNSCs) and normal human astrocytes (NHA). Twelve compounds were identified in the primary screen to be specific in regard to NSCs. Of these, three compounds (AGSC9, AGSC11, AGSC12) showed enhanced specificity in regard to NSCs and NHAs. Future studies will aim to identify molecular pathways targeted by these compounds and determine their effects on tumor progression and animal survival in vivo.

Competition history

• AJAS 2020 Category not listed

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