Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-03-30 | GSE131102 | GEO
Project description:BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. The most prominent and consistent synergy was observed with CDK4/6 inhibitors and paclitaxel. We also uncovered functional similarities and differences between BBD proteins BRD2, BRD4, and BRD7, whereas deletion of BRD2 and BRD4 enhances sensitivity to BBDIs, BRD7 loss leads to resistance. Lastly, single cell RNA-seq and cellular barcoding analysis of BBDI responses in sensitive and resistant cell lines highlight heterogeneity among samples and demonstrate that BBDI resistance can be both pre-existing and acquired.
2020-03-30 | GSE131030 | GEO
Project description:BET bromodomain inhibitors (BBDIs) are candidate therapeutic agents for triple-negative breast cancer (TNBC) and other cancer types, but inherent and acquired resistance to BBDIs limits their potential clinical use. Using CRISPR and small-molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance, we identified synthetic lethal interactions with BBDIs and genes that, when deleted, confer resistance. We observed synergy with regulators of cell cycle progression, YAP, AXL, and SRC signaling, and chemotherapeutic agents. We also uncovered functional similarities and differences among BRD2, BRD4, and BRD7. Although deletion of BRD2 enhances sensitivity to BBDIs, BRD7 loss leads to gain of TEAD-YAP chromatin binding and luminal features associated with BBDI resistance. Single-cell RNA-seq, ATAC-seq, and cellular barcoding analysis of BBDI responses in sensitive and resistant cell lines highlight significant heterogeneity among samples and demonstrate that BBDI resistance can be pre-existing or acquired.
| S-EPMC7306005 | biostudies-literature
Project description:BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. The most prominent and consistent synergy was observed with CDK4/6 inhibitors and paclitaxel. We also uncovered functional similarities and differences between BBD proteins BRD2, BRD4, and BRD7, whereas deletion of BRD2 and BRD4 enhances sensitivity to BBDIs, BRD7 loss leads to resistance. Lastly, single cell RNA-seq and cellular barcoding analysis of BBDI responses in sensitive and resistant cell lines highlight heterogeneity among samples and demonstrate that BBDI resistance can be both pre-existing and acquired.
2020-03-30 | GSE131135 | GEO
Project description:BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. The most prominent and consistent synergy was observed with CDK4/6 inhibitors and paclitaxel. We also uncovered functional similarities and differences between BBD proteins BRD2, BRD4, and BRD7, whereas deletion of BRD2 and BRD4 enhances sensitivity to BBDIs, BRD7 loss leads to resistance. Lastly, single cell RNA-seq and cellular barcoding analysis of BBDI responses in sensitive and resistant cell lines highlight heterogeneity among samples and demonstrate that BBDI resistance can be both pre-existing and acquired.
2020-03-30 | GSE131099 | GEO
Project description:BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. The most prominent and consistent synergy was observed with CDK4/6 inhibitors and paclitaxel. We also uncovered functional similarities and differences between BBD proteins BRD2, BRD4, and BRD7, whereas deletion of BRD2 and BRD4 enhances sensitivity to BBDIs, BRD7 loss leads to resistance. Lastly, single cell RNA-seq and cellular barcoding analysis of BBDI responses in sensitive and resistant cell lines highlight heterogeneity among samples and demonstrate that BBDI resistance can be both pre-existing and acquired.
2020-03-30 | GSE131097 | GEO
Project description:BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. The most prominent and consistent synergy was observed with CDK4/6 inhibitors and paclitaxel. We also uncovered functional similarities and differences between BBD proteins BRD2, BRD4, and BRD7, whereas deletion of BRD2 and BRD4 enhances sensitivity to BBDIs, BRD7 loss leads to resistance. Lastly, single cell RNA-seq and cellular barcoding analysis of BBDI responses in sensitive and resistant cell lines highlight heterogeneity among samples and demonstrate that BBDI resistance can be both pre-existing and acquired.
2020-03-30 | GSE131091 | GEO
Project description:BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. The most prominent and consistent synergy was observed with CDK4/6 inhibitors and paclitaxel. We also uncovered functional similarities and differences between BBD proteins BRD2, BRD4, and BRD7, whereas deletion of BRD2 and BRD4 enhances sensitivity to BBDIs, BRD7 loss leads to resistance. Lastly, single cell RNA-seq and cellular barcoding analysis of BBDI responses in sensitive and resistant cell lines highlight heterogeneity among samples and demonstrate that BBDI resistance can be both pre-existing and acquired.
2020-03-30 | GSE131026 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-01-07 | E-GEOD-63584 | biostudies-arrayexpress
Project description:Synthetic lethal and resistance interactions with BET bromodomain inhibitors
| PRJNA542697 | ENA