The targeting of oncogenic ‘driver’ kinases with small molecule inhibitors has proven to be a highly effective therapeutic strategy in selected non-small cell lung cancer (NSCLC) patients. However, acquired resistance to targeted therapies invariably arises and is a major limitation to patient care. ROS1 fusion proteins are a recently described class of oncogenic driver, and NSCLC patients that express these fusions generally respond well to ROS1-targeted therapy. In this study, we sought to determine mechanisms of acquired resistance to ROS1 inhibition. To accomplish this, we generated a ROS1 inhibition-resistant derivative of the initially sensitive NSCLC cell line HCC78.
Resistance to ROS1 inhibition mediated by EGFR pathway activation in non-small cell lung cancer.
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View SamplesSensitive versus Resistant patient-derived colorectal cancer tumor xenografts with PIK3CA mutant against saracatinib (AZD0530)
Common PIK3CA mutants and a novel 3' UTR mutation are associated with increased sensitivity to saracatinib.
Specimen part
View SamplesTumors from pancreatic cancer specimens obtained at surgery were used for efficacy testing and biologic analysis
Coordinated epidermal growth factor receptor pathway gene overexpression predicts epidermal growth factor receptor inhibitor sensitivity in pancreatic cancer.
No sample metadata fields
View SamplesRigosertib treatment of head and neck squamous cell cancer
The dual pathway inhibitor rigosertib is effective in direct patient tumor xenografts of head and neck squamous cell carcinomas.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A comprehensively characterized cell line panel highly representative of clinical ovarian high-grade serous carcinomas.
Sex, Specimen part, Disease
View SamplesThis study aimed to generate a new panel of comprehensively, genomically characterized high-grade serous ovarian carcinoma (HGSOC) cell line and xenograft models. Multidimensional genomic data were generated and compared between cell lines/xenografts and the tumours they were derived from, indicating the cell lines/xenografts are highly similar to their patient-matched tumours. Cell line/xenograft data were also compared to TCGA ovarian tumours to show the cell lines are good models of clinical HGSOC.
A comprehensively characterized cell line panel highly representative of clinical ovarian high-grade serous carcinomas.
Sex, Disease
View SamplesUncontrolled Transforming growth factor-beta (TGF) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGF-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGF has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGF-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGF-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGF-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGF, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGF signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGF repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGF signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms.
The transcriptional regulators TAZ and YAP direct transforming growth factor β-induced tumorigenic phenotypes in breast cancer cells.
Cell line, Treatment
View SamplesWhe embryonic stem cells are in vitro expanded threir telomereres lengthen, in the absence of genetic manipulations, concomitant with the loss of heterochromatic marks. In order to analyze whether there would be changes in gene expression during in vitro expansion we performed RNA-seq and found no substantial differences in gene expression at passage 6 or 16. Overall design: Embryonic stem (ES) cells were derived from blastocysts expressing GFP in the Rosa26 locus. Four independent lines of ES were in vitro expanded to passage 16. Total RNA was extracted from each independent clones, RNA was extracted and prepared for RNA-seq.
Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Lhx5 controls mamillary differentiation in the developing hypothalamus of the mouse.
Specimen part, Treatment
View SamplesLhx5 mutant mouse embryos show loss of a neuronal nucleus of the brain called the mamillary body and essential for the formation of memories. We wanted to identify the genes that are responsible for the normal development of the mammillary body.
Lhx5 controls mamillary differentiation in the developing hypothalamus of the mouse.
Specimen part
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