Abstract
Glioblastoma is the most malignant and fatal of all primary brain tumors. Each year in the United States, about 22,000 cases of glioma are diagnosed and about 70% of these patients die. The current treatment modality options available for glioma patients are limited to temozolomide, radiation, and surgery. The poor outcome with these treatment options has necessitated the search for a better chemotherapeutic strategy to improve patient outcomes. In a previous study, a genome-scale clustered regularly interspaced short palindromic repeats (CRISPR) screen in glioblastoma was performed under human type II topoisomerase (TOP2) poison selection and found that various aminoacyl tRNA synthetases (AARS) were the most enriched in our screen. This high expression of AARS was validated by western blot and the gliomas were treated with sub-nanomolar doses of AARS inhibitors. Our results showed that AARS inhibitor treatment effectively killed 75 to 90% of the tumors within 72 h and that this killing is independent of DNA damage repair machinery. Taken together, the findings suggest that application of AARS inhibitors might be curative for glioma, but more experimental in-vivo tests will be needed to validate this. Key words: Borrelidin, mupirocin.
Highlights
According to surveillance epidemiology end result programme (SEER) (Ostrom et al, 2018), about 23,820 cases of brain tumor are diagnosed annually in the US. 17,760 of the affected patients die, which is approximately 70% of the cases, making glioblastoma a lethal tumor, and among brain tumors, the most malignant
aminoacyl tRNA synthetases (AARS) is expressed in glioblastoma and its high expression is associated with poor survival outcome
Since AARS has been shown to be expressed in other tumors, we explored if it is highly expressed in glioblastoma
Summary
According to surveillance epidemiology end result programme (SEER) (Ostrom et al, 2018), about 23,820 cases of brain tumor are diagnosed annually in the US. 17,760 of the affected patients die, which is approximately 70% of the cases, making glioblastoma a lethal tumor, and among brain tumors, the most malignant. According to surveillance epidemiology end result programme (SEER) (Ostrom et al, 2018), about 23,820 cases of brain tumor are diagnosed annually in the US. 17,760 of the affected patients die, which is approximately 70% of the cases, making glioblastoma a lethal tumor, and among brain tumors, the most malignant. Aminoacyl tRNA synthetase is a very important enzyme which ensures fidelity in the transmission of genetic information. They play a key role in the loading of amino acids unto the charged tRNA, which transfers it to ribosomes for decoding of the information (Walter, 2017; Carter and Wolfenden, 2015).
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