GEO DataSets

(Submitter supplied) Pan-HER TKI neratinib has demonstrated clinical activity in patients with HER2-mutant cancers. However responses are heterogenoeus and not generally prolonged, suggesting de-novo and acquired resistance to neratinib. To study mechanisms of resistance to neratinib we generated neratinib resistant cells by gradual dose escalation until resistance was achieved and performed various analyses including RNAseq.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21290

24 Samples

Download data: TXT

(Submitter supplied) We conducted RNA sequencing of MM134 lobular cell line expressing HER2 WT and L755S cells grown in low estrogen conditions followed by Gene Set Enrichment Analysis (GSEA) to identify altered gene expression pathways in L755S cells. mTOR (also called MTORC1) signaling was the top significantly up-regulated pathway in HER2 L755S cells as compared to HER2 WT cells

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

4 Samples

Download data: RESULTS

(Submitter supplied) In metastatic breast cancer, HER2 activating mutations frequently co-occur with mutations in the PIK3CA, TP53, or E-cadherin genes. Of these co-occurring mutations, HER2 and PIK3CA mutations are the most prevalent gene pair, with approximately 40% of HER2 mutated breast cancers also having activating mutations in PIK3CA. To study the effects of co-occurring HER2 and PIK3CA mutations, we bred genetically engineered mice with the HER2V777L; PIK3CAH1047R transgenes (HP mice) and studied the resulting breast cancers both in vivo as well as ex vivo using cancer organoids.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

16 Samples

Download data: CSV, TSV

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

Organism:

Homo sapiens

Type:

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

Platform:

GPL18573

64 Samples

Download data: BW

(Submitter supplied) In a 3D coculture with stroma cells derived from breast cancer patients’ brain metastasis, HER2+ breast cancer cells were protected from HER2-targeted therapies, particularly the EGFR/HER2 small molecule inhibitor neratinib. To get insight into how this protection arises, a Synthetic Notch (SynNotch) reporter model allowed to study the effect of direct contact between stroma and cancer cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

40 Samples

Download data: CSV

(Submitter supplied) In a 3D coculture with stroma cells derived from breast cancer patients’ brain metastasis, HER2+ breast cancer cells were protected from HER2-targeted therapies, particularly the EGFR/HER2 small molecule inhibitor neratinib. To get insight into how this protection arises, ATAC-seq on coculture cells with or without neratinib as performed.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

24 Samples

Download data: BW

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

Organism:

Homo sapiens

Type:

Other; Expression profiling by high throughput sequencing

Platform:

GPL21290

24 Samples

Download data

(Submitter supplied) Recent studies suggested that crosstalk between ERα and EGFR/HER2 pathways plays a critical role in mediating endocrine therapy resistance. Several targeting EGFR/HER2 signaling inhibitors including FDA-approved lapatinib and gefitinib as well as a novel dual tyrosine kinase inhibitor (TKI) sapitnib showed greater inhibitory efficacies. However, how a 3D chromatin landscape of the response to the inhibition to EGFR/HER2 pathway remains to be elucidated. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21290

18 Samples

Download data: TXT, XLSX

(Submitter supplied) Recent studies suggested that crosstalk between ERα and EGFR/HER2 pathways plays a critical role in mediating endocrine therapy resistance. Several targeting EGFR/HER2 signaling inhibitors including FDA-approved lapatinib and gefitinib as well as a novel dual tyrosine kinase inhibitor (TKI) sapitnib showed greater inhibitory efficacies. However, how a 3D chromatin landscape of the response to the inhibition to EGFR/HER2 pathway remains to be elucidated. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL21290

6 Samples

Download data: XLSX

(Submitter supplied) We developed a novel computational model, HiSIF (Hi-C Significant Interacting Fragments), which uses a Poisson Mixture Model (PMM) with a power-law decay background. We compared its performance to some existing programs with publicly available Hi-C data, and then applied it to in situ Hi-C data in breast cancer sensitive and resistant cells.

Organism:

Homo sapiens

Type:

Other

Platform:

GPL21290

4 Samples

Download data: TXT

(Submitter supplied) HER2 targeting with trastuzumab has changed the prognosis of breast cancer patients carrying amplification and/or overexpression of this oncogene. Despite this progress, however, resistance to trastuzumab occurs in the vast majority of patients. Newer anti-HER2 therapies, like the dual tyrosine-kinase inhibitor (TKI) lapatinib, show antitumor activity in a limited proportion of patients, indicating that HER2 can be still exploited as a target after trastuzumab failure. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4133

2 Samples

Download data: TXT

(Submitter supplied) We report RNA sequencing data of trastuzumab plus pertuzumab-refractory tumor in a mouse xenograft model.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

2 Samples

Download data: TXT

(Submitter supplied) We report RNA sequencing data of T-DM1-refractory tumor in a mouse xenograft model.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

2 Samples

Download data: TXT

(Submitter supplied) Despite effective strategies, therapy resistance in HER2+ breast cancer remains a challenge. While the Mevalonate pathway (MVA) is suggested to promote cell growth and survival, including in HER2+ models, its potential role in resistance to HER2-targeted therapy is unknown. Using HER2+ breast cancer parental (P) cell models (AU565, SKBR3, and UACC812), we have established anti-HER2-resistant derivatives made resistant to lapatinib (LR) or lapatinib plus trastuzumab (LTR). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

15 Samples

Download data: TXT

(Submitter supplied) Drug treatment-induced transcriptional changes in HCC1954 cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

12 Samples

Download data: XLS

(Submitter supplied) Purpose: Use next generation sequencing to determine which CRISPR knockouts confer resistance to EGFR inhibitors and to determine which cellular pathways get upregulated in response to neratinib.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL11154 GPL18573 GPL15520

29 Samples

Download data: RESULTS, TXT