GEO DataSets

(Submitter supplied) Purpose: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole was approved for treatment of ER+ advanced breast cancer, and other CDK4/6 inhibitors are being investigated in combination with different endocrine treatments. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

26 Samples

Download data: CEL

(Submitter supplied) Resistance to aromatase inhibitor (AI) treatment and combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) are crucial clinical challenges in treating estrogen receptor-positive (ER+) breast cancer. Understanding the resistance mechanisms and identifying reliable predictive biomarkers and novel treatment combinations to overcome resistance are urgently needed. Herein, we show that upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with adaptation and resistance to AI-monotherapy and combined CDK4/6i and ET in ER+ advanced breast cancer. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17586

9 Samples

Download data: CEL, TXT, XLSX

(Submitter supplied) Here we characterise the response of models of ER-positive breast cancer to treatment with the small molecule MDM2 inhibitor NVP-CGM097, a dihydroisoquinolinone derivative currently evaluated in a phase I clinical trial. We show that NVP-CGM097 reduces tumour cell viability of in vitro and in vivo models of endocrine sensitive, endocrine resistant and palbociclib (CDK4/6 inhibitor) resistant p53 wildtype (p53wt) ER-positive breast cancer. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

29 Samples

Download data: CSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome variation profiling by SNP array; SNP genotyping by SNP array

Platforms:

GPL6801 GPL10558

31 Samples

Download data: CEL, CHP

(Submitter supplied) Combination of CDK4/6 inhibitors and endocrine therapy has been shown to improve clinical outcome in advanced estrogen receptor-positive breast cancer. However, not all patients will benefit and relapse is inevitable making the identification of new therapeutic strategies/biomarkers of particular importance.

Organism:

Homo sapiens

Type:

Genome variation profiling by SNP array; SNP genotyping by SNP array

Platform:

GPL6801

8 Samples

Download data: CEL, CHP

(Submitter supplied) Combination of CDK4/6 inhibitors and endocrine therapy has been shown to improve clinical outcome in advanced estrogen receptor-positive breast cancer. However, not all patients will benefit and relapse is inevitable making the identification of new therapeutic strategies/biomarkers of particular importance.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

23 Samples

Download data: TXT

(Submitter supplied) Phosphoinositide-3-kinase/protein-kinaseB/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling plays an important role in breast cancer (BC). Its interaction with estrogen receptor (ER) signalling becomes more complex and inter-dependent with acquired endocrine resistance. Targeting mTOR combined with endocrine therapy has shown clinical utility, however, a negative feedback-loop exists downstream of PI3K/AKT/mTOR. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

12 Samples

Download data: TXT

(Submitter supplied) A large-panel gene expression analysis was conducted to identify biomarkers associated with the effectiveness of adding palbociclib to fulvestrant

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

302 Samples

Download data: CSV

(Submitter supplied) Estrogen receptor positive (ER+) breast cancers that develop resistance to therapies that target the ER are the most common cause of breast cancer death. Beyond mutations in ER, which occur in 25-30% of patients treated with aromatase inhibitors (AIs), our understanding of clinical mechanisms of resistance to ER-directed therapies remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to ER-directed agents, including AIs, tamoxifen, and fulvestrant. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

864 Samples

Download data: TXT

(Submitter supplied) The goal of this study is to measure gene expression changes resulting over time of palbociclib treatment of T47D, MCF7, and CAMA1 ER+ breast cancer cell lines.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

15 Samples

Download data: XLSX

(Submitter supplied) Activation of the PI3K pathway in estrogen receptor α (ER)-positive (+) breast cancer is associated with reduced ER expression and activity, luminal B subtype, and poor outcome. PTEN is a negative regulator of the PI3K pathway typically lost in ER-negative (-) breast cancer. To clarify the effect of PTEN down-regulation on the response of ER+/HER2- breast cancer to endocrine therapy, we established reduced PTEN cell models using inducible knockdown. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL9052

2 Samples

Download data: FPKM_TRACKING

(Submitter supplied) The results from our study have identified two clinically relevant, divergent and druggable pathways (DNA repair and STAT3) that can be targeted in combination to effectively combat drug resistance. We also found that the same pathways that were deregulated in palbociclib-resistant cells were also altered in tumor samples obtained from patients who progressed while on palbociclib and endocrine therapy

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

7 Samples

Download data: XLSX

(Submitter supplied) gene expression analysis ussing microarray analysis of a subset of primary tumors collected from patients that participated in the CONFIRM phase III study, which randomized post menopausal patients with ER+ metastatic breast cancer to fulvestrant 500mg and fulvestrant 250mg.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17586

113 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17303

15 Samples

Download data: BED, BW

(Submitter supplied) We performed SMAD2 ChIP-seq analysis in T47D cells with/without Palbociclib treatment. To validate whether the changes in SMAD2 binding to the genome indeed resulted in changes in target gene expression, we performed RNA-seq transcriptome analyses in T47D with/without ActA stimulation and Palbo treatment.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17303

4 Samples

Download data: BW, FPKM_TRACKING

(Submitter supplied) Inhibitors for cyclin-dependent kinase (CDK) 4 and CDK6 have been established as effective therapeutic options for hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Although the CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we have focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor Palbociclib and Activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Mechanistically, Palbociclib enhanced SMAD2 binding to the genome through inhibiting linker phosphorylation of the SMAD2 protein by CDK4/6. Comparison of the SMAD2 ChIP-seq data of T47D with those of a triple-negative breast cancer cell line Hs578T indicated that Palbociclib augments different SMAD2-mediated program defined based on types of cells, and enhances SMAD2 binding to the target regions on the genome without affecting its binding pattern. Collectively, the CDK4/6 inhibitor facilitates the cytostatic effects of Activin-SMAD2, while it also enhances its tumor promoting effects depending on types of breast cancer.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17303

6 Samples

Download data: BED, BW

(Submitter supplied) Inhibitors for cyclin-dependent kinase (CDK) 4 and CDK6 have been established as effective therapeutic options for hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Although the CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we have focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor Palbociclib and Activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Mechanistically, Palbociclib enhanced SMAD2 binding to the genome through inhibiting linker phosphorylation of the SMAD2 protein by CDK4/6. Comparison of the SMAD2 ChIP-seq data of T47D with those of a triple-negative breast cancer cell line Hs578T indicated that Palbociclib augments different SMAD2-mediated program defined based on types of cells, and enhances SMAD2 binding to the target regions on the genome without affecting its binding pattern. Collectively, the CDK4/6 inhibitor facilitates the cytostatic effects of Activin-SMAD2, while it also enhances its tumor promoting effects depending on types of breast cancer.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17303

5 Samples

Download data: BED, BW

(Submitter supplied) Transcriptional profiling of breast cell lines comparing breast cell line mixed reference with individual breast cell lines. Goal was to characterize breast cell line subtypes.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL7264

51 Samples

Download data: TXT

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

SNP genotyping by SNP array; Genome variation profiling by SNP array

Platform:

GPL6801

2 Samples

Download data: CEL, CNCHP, TXT

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

24 Samples

Download data: IDAT