Similar Datasets
Project description:To investigate the effect of single and combination treatments in breast cancer, we performed transcriptome profiling using bulk RNAseq
2025-12-15 | GSE255765 | GEO
Project description:MCF-7 ESR1 drug response scRNA
| PRJNA1076489 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-12-15 | GSE255767 | GEO
Project description:MCF-7 ESR1 drug response bulk RNA
| PRJNA1076488 | ENA
Project description:Previously, we have proved the NOS2 and COX2 genes play an important role in ER-negative breast cancer. In this study, we utilized the scRNAseq technique to investigate how cancer cells react to cytokines with and without IFNG combination treatments.
2023-12-31 | GSE232567 | GEO
Project description:The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.
2024-06-01 | GSE266932 | GEO
Project description:The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and endocrine therapy resistance remain incompletely understood. Here, we reported that circPVT1, a circular RNA generated from lncRNA PVT1, is highly expressed in ERalpha-positive breast cancer cell lines and tumor samples, which is functionally important in promoting ERalpha-positive breast tumorigenesis and endocrine therapy resistance. CircPVT1 acts as a competing endogenous RNA (ceRNA) to sponge miR-181a-2-3p, promoting the expression of ESR1 and downstream ERalpha-target genes and breast cancer cell growth. Meanwhile, circPVT1 directly interacts with MAVS to disrupt the RIGI-MAVS complex formation, inhibiting type I interferon (IFN) signaling pathway and anti-tumor immunity. The dual mechanisms both contribute to ERα-positive breast tumorigenesis. Anti-sense oligonucleotides (ASO) targeting circPVT1 was shown to inhibit ERalpha-positive breast cancer cell and tumor growth, and could re-sensitize tamoxifen-resistant ERalpha-positive breast cancer cells to tamoxifen treatment. Taken together, our data demonstrated that circPVT1 can work through both ceRNA and protein scaffold mechanisms to promote cancer, and in particular, circPVT1 may serve as a diagnosis biomarker and therapeutic target for ERalpha-positive breast cancer in the clinic.
2023-02-06 | GSE220776 | GEO
Project description:Estrogen receptor alpha (ER) is a critical driver of tumorigenesis and tumor progression in most breast cancers. Endocrine therapies targeting the ER are the cornerstone treatments in hormone receptor-positive breast cancer. Resistance to these therapies poses a significant clinical challenge and is due to diverse mechanisms. Some of these mechanisms, particularly through estrogen independent activity and the ESR1 mutations, remain dependent on the estrogen axis providing a rationale for the development of next-generation endocrine therapies. This study investigates the preclinical efficacy of imlunestrant, a next-generation oral selective estrogen receptor degrader, in ER-positive breast cancer pre-clinical models, including models harboring the Y537S ESR1 mutation, a prevalent and potent ER activating mutation. Imlunetsrant demonstrated pure antagonistic activity and effective degradation of both wild-type and mutant ER, significantly suppressing cell growth. In vivo, imlunestrant outperformed fulvestrant leading to tumor regression in a patient derived xenograft harboring the Y537S ESR1 mutation. Cyclic multiplexed immunofluorescence and transcriptomic analysis revealed enhanced cell cycle arrest and downregulation of estrogen-responsive genes with imlunestrant treatment. Additionally, a genome wide CRISPR knock-out screen identified several vulnerabilities that were either persistent or gained after imlunestrant treatment, which provides a rational for future studies of combination treatments with imlunestrant. In summary, these results highlight the on target and selective potent activity of imlunestrant, which can circumvent resistance engendered by the Y537S ESR1 mutation and support the clinical development of imlunestrant.
2025-04-18 | GSE295024 | GEO
Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with very limited therapeutic options. We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell cycle arrest and ultimately cell death. However, the underlying mechanisms by which co-inhibition of EGFR and ROCK induces cell death remain unclear. To investigate the synergistic effect of the combination treatment on TNBC cells, in the present study we applied a mass spectrometry-based proteomic approach to identify proteins altered upon single and combination treatments.
2019-12-04 | PXD013821 | Pride