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Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing.\u00a0<jats:italic>Methods<\/jats:italic> The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-\u03baB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical library of &gt;\u20091500 FDA-approved drugs and &gt;\u200925,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins.\u00a0<jats:italic>Results<\/jats:italic> Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier.\u00a0<jats:italic>Conclusions<\/jats:italic> In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.<\/jats:p>","DOI":"10.1007\/s10637-020-01037-7","type":"journal-article","created":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T22:02:38Z","timestamp":1607810558000},"page":"670-685","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma"],"prefix":"10.1007","volume":"39","author":[{"given":"Mohamed E. 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NCT02104882 (registration date: 03\/26\/2014) (). INTRAGO was approved by the local ethics committee (Medical Ethics Commission II of the Faculty of Mannheim, University of Heidelberg 2013-548S-MA) and the Federal Office of Radiation Protection (Z 5-2246\/2-2013-063).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed written consent had been given by the patient that the data are allowed to be scientifically used and published (dated: January 26, 2016).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"All authors declare there is no conflict of interest. However, patent application #EP18211231 \u201cA method to determine agents for personalized use\u201d is disclosed.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}