Systematic drug sensitivity testing reveals synergistic growth inhibition by dasatinib or mTOR inhibitors with paclitaxel in ovarian granulosa cell tumor cells

摘要: Abstract Objective Resistance to standard chemotherapy poses a major clinical problem in the treatment of ovarian cancer patients. Adult-type granulosa cell tumor (AGCT) is unique subtype for which efficient options are lacking advanced disease. To this end, systematic drug response and transcriptomics profiling were performed uncover new therapy AGCTs. Methods The responses three primary four recurrent AGCTs 230 anticancer compounds screened vitro using sensitivity resistance testing (DSRT) platform, coupled with mRNA sequencing. compared those human luteal cells bone marrow mononuclear cells. Results Patient-derived AGCT showed selective Src family tyrosine kinase inhibitor dasatinib. A combination either dasatinib or an mTOR-inhibitor everolimus paclitaxel resulted synergistic inhibition viability. key targets members mTOR pathway constantly expressed at protein levels, indicating multikinase signal addictions Transcriptomic characterization tumors revealed no known oncogenic mutations, suggesting that was rather conveyed by target expression. Conclusions We used functional approach reveal novel gynecological cancer. synergy found between taxanes inhibitors warrants further investigations these combinations relapsed aggressive demonstrate high-throughput screening molecular can provide effective options.