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DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer

ABSTRACT: DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer

PROVIDER: PRJNA966201 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24412600_1.fastq.gz	Fastqsanger.gz
	SRR24412600_2.fastq.gz	Fastqsanger.gz
	SRR24412601_1.fastq.gz	Fastqsanger.gz
	SRR24412601_2.fastq.gz	Fastqsanger.gz
	SRR24412602_1.fastq.gz	Fastqsanger.gz

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DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy resistance in HER2+ breast cancer [MDA]

Project description:DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy resistance in HER2+ breast cancer [MDA]

| PRJNA966202 | ENA

DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy resistance in HER2+ breast cancer [BT474]

Project description:DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy resistance in HER2+ breast cancer [BT474]

| PRJNA966203 | ENA

DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy resistance in HER2+ breast cancer [MDA]

Project description:To investigate transcriptomic changes regulated by DUSP6 in a HER2+ breast cancer cell line We performed gene expression profiling analysis using data obtained from RNA-seq of SCR vs DUSP6 KD MDA-MB-453 cells

2024-04-13 | GSE231524 | GEO

DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy resistance in HER2+ breast cancer [BT474]

Project description:To investigate transcriptomic changes during development of resistance to lapatinib in a HER2+ breast cancer cell line We performed gene expression profiling analysis using data obtained from RNA-seq of 4 different stage of development of lapatinib resistance in a HER2+ breast cancer cell line

2024-04-13 | GSE231525 | GEO

DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer

Project description:Despite clinical benefits of tyrosine kinase inhibitors (TKIs) in cancer, most tumors can reactivate proliferation under TKI therapy. Here we present transcriptional profiling of HER2+ breast cancer cells transitioning from dormant drug tolerant cells to re-proliferating cells under continuous HER2 inhibitor (HER2i) therapy. Focusing on phosphatases, expression of dual-specificity phosphatase DUSP6 was found inhibited in dormant cells, but strongly induced upon re-growth. DUSP6 expression also selectively associated with poor patient survival in HER2+ breast cancers. DUSP6 overexpression conferred apoptosis resistance, whereas its pharmacological blockade prevented therapy tolerance development under HER2i therapy. DUSP6 targeting also synergized with clinically used HER2i combination therapies. Mechanistically DUSP6 is a positive regulator of HER3 expression, and its impact on HER2i tolerance was mediated by neuregulin-HER3 axis. In vivo, genetic targeting of DUSP6 reduced tumor growth in brain metastasis model, whereas its pharmacological targeting induced synthetic lethal therapeutic effect in combination with HER2i. Collectively this work demonstrates that DUSP6 drives escape from HER2i-induced dormancy, and that DUSP6 is a druggable target to overcome HER3-driven TKI resistance.

| S-SCDT-10_1038-S44321-024-00088-0 | biostudies-other

MCF10A cells expressing HER2 and HER3 and grown in three-dimensional cultures

2012-09-01 | GSE37009 | GEO

MCF10A cells expressing HER2 and HER3 and grown in three-dimensional cultures

Project description:The tyrosine kinase receptors HER2 and HER3 play an important role in breast cancer. The HER2/HER3 heterodimer is a critical oncogenic unit associated with reduced relapse-free and decreased overall survival. We provide gene expression profile of the mammary epithelial cells MCF10A expressing HER2, HER3 or HER2/HER3 and grown in three-dimensional cultures for 15 days in the presence of heregulin, a known HER3-ligand that stabilizes and activates the HER2/HER3 heterodimer. The mammary epithelial cells MCF10A were transduced with retroviral vectors expressing HER2, HER3 or both. Cells from each group were grown for 15 days in three-dimensional cultures. At the end of the experiment, RNA was extracted for gene expression analysis.

2012-09-01 | E-GEOD-37009 | biostudies-arrayexpress

DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer

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

2024-04-12 | GSE231526 | GEO

DNA methylation pattern between patients with HER3+ and HER3- brain metastases

Project description:HER3 (ErbB3) belongs to a family of receptor tyrosine kinases together with the known oncogenes EGFR and HER2. Recently, antibody drug conjugates (ADCs) targeting these receptors showed promising clinical activity in extracranial malignancies of breast and lung cancer. We aimed to investigate HER3 expression in breast and lung cancer brain metastases (BM) as the basis for future clinical trial design. Illumina MethylationEPIC 850k microarrays were used to analyze genome-wide DNA methylation patterns of HER3-positive (n=43) and HER3-negative (n=28) BM.

2023-03-31 | GSE220826 | GEO

The Neuregulin 1-HER axis as a key mediator of hyperglycemic memory effects in breast cancer

Project description:Poor outcomes in diabetic patients are observed across a range of human tumors, suggesting that cancer cells develop unique characteristics under diabetic conditions. Cancer cells exposed to hyperglycemic insults acquire permanent aggressive traits of tumor growth, even after a return to euglycemic conditions. Comparative genome-wide mapping of hyperglycemia-specific open chromatin regions and concomitant mRNA expression profiling revealed that neuregulin-1 gene, an established endogenous ligand for the HER3 receptor, is activated through a putative distal enhancer. Our findings highlight the targeted inhibition of NRG1-HER3 pathways as a potential target for the treatment breast cancer patients with associated diabetes

2012-09-19 | GSE40949 | GEO

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