Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA314235 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Expression profiling of response to first-line aromatase inhibitor therapy
| PRJNA178932 | ENA
Project description:Understanding the complex molecular mechanisms underlying resistance to endocrine therapy is a major challenge in the treatment of estrogen receptor-positive (ER+) breast cancers. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) signaling via the receptor tyrosine kinase RET promotes estrogen independent activation of ER. Here we have addressed the relevance of GDNF-RET signaling in response to aromatase inhibitor treatment and explored the efficacy of using RET inhibitors in breast cancer models of aromatase inhibitor response and resistance. A GDNF-response gene set, identified from gene expression profiling, was demonstrated to be an independent prognostic marker of poor patient outcome and, importantly, to be predictive of poor response to aromatase inhibitor treatment and development of resistance. The relevance of these findings was validated first by demonstrating an association of RET protein expression in an independent cohort of aromatase inhibitor resistant patient samples. Second, in in vitro models, GDNF-mediated RET signaling was demonstrated to enhance the survival of aromatase inhibitor resistant cells and to increase resistance in aromatase inhibitor sensitive cells. These effects could be reversed by targeting GDNF/RET signaling with the RET selective inhibitor NVP-BBT594 thus identifying GDNF-RET signaling as a potential therapeutic target, particularly in breast cancers resistant to aromatase inhibitors.<br>MCF7 cells were E2-deprived by culturing in phenol red-free RPMI 1640 supplemented with 10% DCC for 3 days and then serum-starved overnight in the presence or absence of fulvestrant (ICI182,780) (100 nM). The following day, cells were treated with GDNF (20 ng/ml) for 0, 4, 8, 24 and 48 hours in the presence or absence of fulvestrant (ICI182,780) (100 nM).
2013-01-17 | E-MEXP-3662 | biostudies-arrayexpress
Project description:The gene expression of aromatase-inhibitor-resistant cell line
| PRJNA222900 | ENA
Project description:Estrogen Receptor Positive Breast Cancer Aromatase Inhibitor Response Study
| PRJNA157235 | ENA
Project description:Estrogen Receptor Positive Breast Cancer Aromatase Inhibitor Response Study
| PRJNA89531 | ENA
Project description:The goal of the experiment is untargeted metabolomic and shotgun lipidomic profiling of serum samples collected from 50 patients before patients initiated therapy with an aromatase inhibitor and again after 3 months of aromatase inhibitor therapy. Half of the patients discontinued treatment within 6 months because of development of arthralgias during therapy and half remained on therapy for at least 24 months without development of significant arthralgias. We plan to analyse effects of AI therapy on metabolomic and lipidomic profiles, and to investigate associations between changes in profiles and development of symptoms.
2018-08-02 | MSV000082740 | GNPS
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.
2015-08-07 | GSE71791 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:A multiple receptor tyrosine kinase inhibitor, sunitinib, is a first-line therapy for clear cell renal cell carcinoma (CCRCC). Unfortunately, it has the major challenges of low initial response rate and resistance after about one year of treatment. Here we evaluated a microRNA (miRNA) and its target responsible for sunitinib resistance. Using miRNA profiling, we identified miR-96-5p upregulation in tumors from sunitinib-resistant CCRCC patients
2021-12-03 | GSE189331 | GEO
Project description:The main goal of the study is to define miR expression levels related to clinical and biological parameters. Now in particular, miR expression levels of fresh frozen (estrogen receptor-positive) primary tumors were related to PIK3CA genotype and with progression-free survival in breast cancer patients with metastatic breast cancer that received first-line aromatase inhibitor therapy.
2016-03-03 | GSE78870 | GEO