GSE106695 GRHL2 is a key lineage determining factor which collaborates with FOXA1 to establish a targetable collateral pathway in the setting of endocrine therapy-resistant breast cancer

Series Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThe estrogen receptor (ER) is expressed in the majority of luminal breast cancers and inhibition of its transcriptional activity with selective estrogen receptor modulators, selective estrogen receptor degraders and/or aromatase inhibitors is a standard approach used in the management of this disease. Despite the positive clinical impact of these interventions, de novo and acquired resistance limits the therapeutic lifespan of these classes of drugs. Considering what is known about the complex mechanisms that contribute to the development of resistance it is likely that further development of ER-modulators will yield only incremental improvements. Thus, with the view that resistance is inevitable, we undertook the development of a new approach to treat ER-positive breast cancer by identifying and exploiting targetable vulnerabilities that emerge in endocrine therapy resistant disease. Genomic discovery platforms, including DNASeq, ChIPSeq and RNASeq were used to assess the epigenome, targeting global transcription factor binding profile, and transcriptome in cellular models of endocrine therapy sensitive and resistant disease. DNASeq was first used to identify the chromatin state, with a focus on differences, between these two models. Motif enrichment analysis indicated FOXA1 was a candidate transcription factor influencing the chromatin architecture, which was consistent with previously pu...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research