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Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas

GSE255754 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2024/08/28 Platform GPL15433
Summary
High grade gliomas (HGGs) remain highly fatal malignancies with glioblastoma accounting for almost 50% of primary brain malignancies in the elderly. Unfortunately, despite the use of multiple treatment modalities, the prognosis remains poor in this population. Our pre-clinical studies suggest that the expression of CYP19A1, that encodes aromatase, is significantly upregulated in HGGs and that letrozole (LTZ), an FDA approved aromatase inhibitor, has marked activity against HGGs. We conducted a phase 0/I single center clinical trial to assess the tumoral availability, pharmacokinetics (PK), safety and tolerability of LTZ in recurrent HGG patients. Planned dose cohorts included 2.5, 5, 10, 12.5, 15, 17.5 and 20 mg of LTZ administered daily pre- and post-surgery or biopsy. Tumor samples were assayed for LTZ content and relevant biomarkers. LTZ caused dose-dependent inhibition of estradiol synthesis and modulated DNA damage pathways in tumor tissues as evident using RNA-seq analysis.
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Direct links to NCBI, no account and no request form: the whole study as GSE255754_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1076460 and SRA study SRP489687. Searching any of these in the dataset finder brings you back here.

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