N-acetylcysteine overcomes NF1-loss driven resistance to PI3K alpha inhibition in breast cancer [ATAC-seq]

The aim of our study was to investigate PIK3CA collaborative mutations that result in resistance to BYL719, a PI3Ka selective inhibitor. One of the tumor suppressor genes discovered was neurofibromin 1 (NF1). Using shRNA-mediated knockdown and CRISPR/Cas9-mediated knockout of NF1 in murine and human PIK3CAH1047R cell lines and a patient derived xenograft organoid model, we found that NF1 loss reduces sensitivity to PI3Ka inhibition. By looking at differentially expressed genes we wanted to investigate the effect of NF1 KO in T47D cells and if they respond differentially to BYL719 compared to the T47D CTRL cells. Overall design: Overall genomic DNA from 51 resistant and 94 untreated tumors was isolated and processed by splinkerette PCR for NGS-based transposon integration mapping