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• W2897788101 abstract "Steroid hormone receptors (SRs) have a multitude of functions in human biology and disease progression. The SR family of related ligand-activated transcription factors includes androgen, estrogen, glucocorticoid, mineralocorticoid, and progesterone receptors. Antiestrogen or estrogen receptor (ER)-targeted therapies to block ER action remain the primary treatment of luminal breast cancers. Although this strategy is successful, ∼40% of patients eventually relapse due to endocrine resistance. The majority of hormone-independent tumors retain some level of SR expression, but sidestep hormone ablation treatments. SRs are known to crosstalk extensively with kinase signaling pathways, and this interplay has been shown to bypass ER-targeted therapies in part by providing alternative proliferation and survival signals that enable hormone independence. Modified receptors adopt alternate conformations that resist antagonism or promote agonism. SR-regulated transcription and SR-binding events have been classically studied as single receptor events using single hormones. However, it is becoming increasingly evident that individual steroids and SRs rarely act alone. Emerging evidence shows that coexpressed SRs crosstalk with each other in hormone-driven cancers, such as breast and prostate. Crosstalk between related SRs allows them to modulate signaling and transcriptional responses to noncognate ligands. This flexibility can lead to altered genomic binding and subsequent changes in SR target gene expression. This review will discuss recent mechanistic advances in elucidating SR crosstalk and the implications for treating hormone-driven cancers. Understanding this crosstalk (i.e., both opposing and collaborative) is a critical step toward expanding and modernizing endocrine therapies and will ultimately improve patient outcomes." @default.
• W2897788101 created "2018-10-26" @default.
• W2897788101 creator A5042072871 @default.
• W2897788101 creator A5051915371 @default.
• W2897788101 date "2018-10-10" @default.
• W2897788101 modified "2023-10-14" @default.
• W2897788101 title "Deciphering Steroid Receptor Crosstalk in Hormone-Driven Cancers" @default.
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• W2897788101 doi "https://doi.org/10.1210/en.2018-00831" @default.
• W2897788101 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6236424" @default.
• W2897788101 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30307542" @default.
• W2897788101 hasPublicationYear "2018" @default.
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