Effect of BET bromodomain inhibitor and/or mTOR inhibitor on transcriptome of small cell lung cancer patient-derived xenograft LX95 tumors

We report mTOR inhibitor (mTORi) is synergistic with BET inhibitor (BETi) in controlling tumor growth and inducing apoptosis in small cell lung cancer (SCLC) patient-derived xenograft (PDX) models. In this study, we studied impact of different treatment on whole-genome mRNA transcriptome in SCLC PDX tumors. Four different treatments (vehicle control, NHWD870 [BETi; 1.5mg/kg], everolimus [mTORi; 2mg/kg], and the combo [NHWD870 1mg/kg and everolimus 1.5mg/kg] were administered daily for one week in a small cell lung cancer PDX LX-95 model. Tumor cells were isolated from PDX tumors using a magnetic-activated cell sorting method to enrich human tumor cells and total RNA was extracted using the RNeasy Mini Kit (Qiagen). mRNA libraries were constructed and pair-ended sequenced using Illumina high-throughput sequencing technology. The length of sequence reads was 150 bp.The samples have 12 to 129 million pass filter reads with more than 90% of bases above the quality score of Q30. We found BET inhibitor increases expression of RPS6KA2, a gene that mediates crosstalk between MAPK and mTOR pathway. Overall design: mRNA profiles of the LX95 small cell lung cancer PDX after one-week treatment of BET inhibitor and/or mTOR inhibitor