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ChIP-seq: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

ABSTRACT: ChIP-seq: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

PROVIDER: PRJNA786918 | ENA |

REPOSITORIES: ENA

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RNAseq: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

Project description:We carried out a comparative study of the orally bioavailable investigational SERD elacestrant, versus fulvestrant, in models of endocrine sensitive and resistant BC harbouring varying genetic backgrounds. Both drugs showed comparable effects on tumour growth of ER+ patient-derived xenograft models harbouring several ESR1 mutations and elacestrant showed activity after acquired resistance to fulvestrant. Treatment with either drug showed similar impact on ER-cistrome, ER- interactome and suppression of estrogen-regulated genes, confirming the anti-estrogenic activity of elacestrant.

2022-08-01 | GSE190384 | GEO

ChIP-seq: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

2022-08-01 | GSE190385 | GEO

Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

Project description:Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

| PRJNA786914 | ENA

RNAseq: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

Project description:RNAseq: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

| PRJNA786919 | ENA

Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

Project description:Human breast cancer cell lines were cultured in phenol red-free RPMI1640 medium supplemented with 10% fetal bovine serum and 1nM E2. All cell lines were banked in multiple aliquots to reduce the risk of phenotypic drift and identity confirmed using STR. Cells were routinely screened for mycoplasma contamination. Long-term E deprived (LTED) cells modelling resistance to an AI were derived from all parental cell lines as previously described. Two models of MCF7-LTED cells were available: one harbouring a Y537C mutation in ESR1 and the other with wt-ESR1. SUM44-LTED was shown to harbour a natural heterozygous ESR1Y537S mutation. Elacestrant resistant cell lines were generated by growing parental cells (MCF7-LTEDY537C) long-term in the presence of RPMI1640 containing 10% DCC + 0.1nM E2 + 1μM elacestrant. All cell lines were stripped of steroids for 48-72 hours prior to the start of experiments.

2023-03-10 | PXD031377 | Pride

Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-01 | GSE190386 | GEO

Fulvestrant withdrawal from fulvestrant-resistant MCF-7/FR cells

Project description:Fulvestrant withdrawal from fulvestrant-resistant MCF-7/FR cells

| PRJNA497213 | ENA

Fulvestrant withdrawal from fulvestrant-resistant MCF-7/FR cells

Project description:Estrogens have been shown to elicit anti-cancer effects against estrogen receptor alpha (ER)-positive breast cancer. We sought to determine the underlying mechanism of therapeutic response. Response to 17b-estradiol was assessed in ER+ breast cancer models with resistance to estrogen deprivation: WHIM16 patient-derived xenografts, C7-2-HI and C4-HI murine mammary adenocarcinomas, and long-term estrogen-deprived MCF-7 cells. As another means to reactivate ER, the anti-estrogen fulvestrant was withdrawn from fulvestrant-resistant MCF-7 cells. Transcriptional, growth, apoptosis, and molecular alterations in response to ER reactivation were measured. 17b-estradiol treatment and fulvestrant withdrawal induced transcriptional activation of ER, and cells adapted to estrogen deprivation or fulvestrant were hypersensitive to 17b-estradiol. ER transcriptional response was followed by an unfolded protein response and apoptosis. Such apoptosis was dependent upon the unfolded protein response, p53, and JNK signaling. Anti-cancer effects were most evident in models exhibiting genomic amplification of the gene encoding ER (ESR1), suggesting that engagement of ER at high levels is cytotoxic. These data indicate that long-term adaptation to estrogen deprivation or ER inhibition alters sensitivity to ER reactivation. In such adapted cells, 17b-estradiol treatment and anti-estrogen withdrawal hyperactivate ER, which drives an unfolded protein response activation and subsequent growth inhibition and apoptosis. 17b-estradiol treatment should be considered as an alternative therapy for anti-estrogen-resistant disease, particularly in patients with tumors harboring ESR1 amplification or overexpression. Furthermore, therapeutic strategies that enhance an unfolded protein response may enhance the therapeutic effects of ER reactivation.

2019-08-19 | GSE121379 | GEO

Differences in the Transcriptional Response to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer

Project description:Aromatase inhibitors are first-line postmenopausal agents for estrogen receptor alpha (ERa)-positive breast cancer. However, there is considerable response heterogeneity and women frequently relapse. Estrogen deprivation does not completely arrest ERa activity, and transactivation of the unliganded receptor may continue through cross-talk with growth factor pathways. In contrast with aromatase inhibitors, the selective ER downregulator fulvestrant also abrogates ligand-independent ERa activity. The benefit of fulvestrant as an alternative, combination, or sequential therapy to aromatase inhibitor has been reported, but molecular mechanisms underpinning its relative efficacy remain unclear and biomarkers for patient selection are lacking. This study demonstrates, for the first time, that the overall transcriptional response to fulvestrant is of greater magnitude than estrogen deprivation, consistent with its clinical efficacy and more complete blockade of estrogenic signaling. Using a robust integrative approach, we identify a subset of genes differentially affected by fulvestrant that comprises distinct biologic networks, correlates with antiproliferative response, and has potential utility as predictive biomarkers for fulvestrant. Global gene expression profiles from ERα-positive breast carcinomas before and during presurgical treatment with fulvestrant (n = 38) or anastrozole (n = 81), and corresponding in vitro models, were compared. Transcripts responding differently to fulvestrant and estrogen deprivation were identified and integrated using Gene Ontology, pathway and network analyses to evaluate their potential significance. --------------------------------- This represents the data for fulvestrant only

2015-08-07 | E-GEOD-71791 | biostudies-arrayexpress

Differences in the Transcriptional Response to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer

2015-08-07 | GSE71791 | GEO