GEO DataSets

(Submitter supplied) Anticancer drug development is an inefficient process, with potential therapeutics demonstrating a high attrition rate due to lack of efficacy in Phase II/III testing. In an effort to develop improved pre-clinical predictors of efficacy, we and others have turned to testing in genetically engineered murine models (GEMMs) of cancer, which may offer some advantages to in vitro and xenograft systems. Specifically, we assessed the activity of 16 treatment regimens in a Ras-driven, Ink4a/Arf-deficient melanoma GEMM. Like human RAS-mutant melanoma, this GEMM was refractory to standard chemotherapy and single-agent small molecule therapies. Only one regimen exhibited significant anti-tumor activity in this model: combined treatment with AZD6244 (MEK inhibitor) and BEZ235 (dual PI3K/mTOR inhibitor), which produced marked tumor regression and improved survival. Given the surprising activity of the “AZD/BEZ” combination in a melanoma GEMM, we next tested this regimen in a Ras-driven orthotopic-transplant model of “claudin-low” breast cancer, which shares some gene expression features with melanoma. The AZD/BEZ regimen also exhibited significant activity in this related Ras-driven model, leading us to testing in even more diverse GEMMs of basal-like and luminal breast cancer. The AZD/BEZ combination was highly active in each of these distinct breast models, demonstrating equal or greater efficacy compared to any other regimen tested in studies of over 700 tumor-bearing mice. This regimen even exhibited activity in tumors selected for resistance to another effective chemotherapy agent, lapatinib, in HER2+ models. These results demonstrate the utility of credentialed murine models for large-scale efficacy testing of diverse anti-cancer regimens, and predict combinations of PI3K/mTOR and MEK inhibitors will demonstrate anti-tumor activity in a wide-range of human malignancies.

Organism:

Mus musculus

Type:

Expression profiling by array

Platforms:

GPL2881 GPL11383 GPL10732

16 Samples

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(Submitter supplied) Anti-cancer drug testing is challenging, but genetically engineered mouse models (GEMMs) and orthotopic, syngeneic transplants (OSTs) may offer advantages for pre-clinical testing including an intact microenvironment. We examined the efficacy of six chemotherapeutic or targeted anti-cancer drugs, alone and in combination, using over 500 GEMMs/OSTs representing three distinct breast cancer subtypes: Basal-like (C3(1)-T-antigen GEMM), Luminal B (MMTV-Neu GEMM), and Claudin-low (T11/TP53-/- OST). more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL4134

19 Samples

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(Submitter supplied) We used microarrays to assess gene expression in proliferating ovarian cancer cell lines

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

98 Samples

Download data: CEL

(Submitter supplied) Therapeutic targeting of BRAFV600E has shown a significant impact on progression-free and overall survival in advanced melanoma, but only a fraction of patients benefit from these treatments, suggesting that additional signaling pathways involved in melanoma growth/survival need to be identified. In fact MAPK and PI3K/mTOR signaling pathways are constituively activated in most cancers, including melanoma, to sustain the melanoma growth/survival. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

24 Samples

Download data: TXT

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

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

98 Samples

Download data: CEL

(Submitter supplied) Basal gene expression levels were determined by global gene expression profiling of breast cancer cell lines. Molecular subtype was determined using gene expression and HER2 status assesses by HER2 FISH analysis. Keywords: Basal gene expression (no stimulation or timecourse)

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

51 Samples

Download data: CEL

(Submitter supplied) MCF10A cells were then transfected with MEK1(S217S221), HRAS(G12V), and null control vectors Cells were lysed 24 hours post-transfection with collection of total RNA and protein Keywords: Oncogene inducation of gene expression changes

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

17 Samples

Download data: CEL

(Submitter supplied) We used microarrays to profile 30 human primary breast tumors and determine global gene expression patterns and molecular subtypes Keywords: Basal gene expression in human tumor samples

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

30 Samples

Download data: CEL

(Submitter supplied) In an effort to understand the mechanisms of acquired resistance to BRAF inhibitors, we isolated clones that acquired resistance to the BRAF inhibitor GSK2118436 derived from the A375 BRAF V600E mutant melanoma cell line. This resistance clones acquired mutations in NRAS and MEK1. One clones, 16R6-4, acquired two mutations in NRAS – Q61K and A146T. Proliferation and western blot analyses demonstrated that these clones were insensitive to single agent GSK2118436 or GSK1120212 (an allosteric MEK inhibitor) but were sensitive to the combination of GSK2118436 and GSK1120212. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

38 Samples

Download data: CEL

(Submitter supplied) 3 Cell lines from Apc, p53 (AP) GEMMs were compared to 12 cell lines from Apc, Kras, p53 (AKP) GEMMs. Mouse 430 2.0 arrays were used to determine genomic expression differences between the two genotypes (AP and AKP).

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

15 Samples

Download data: CEL, TXT

(Submitter supplied) Purpose: Osteosarcoma (OS) is the most common primary bone malignancy. OS consists of several subtypes including fibroblastic, osteoblastic and chondroblastic OS. We have developed genetically engineered mouse models of human OS that recapitulate two distinct subtypes, fibroblastic (Osx-CreLox p53-/- Rb-/-) and osteoblastic (Osx-Cre shRNA p53-/-) OS. The goal of this study was to identify transcriptional differences that distinguish the two subtypes. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: TXT

(Submitter supplied) In this study, we identified a multi-kinase inhibitor MTX-216 to be efficacious in blocking NF1 loss-of-function melanoma cells. To identify the mechansisms of action of MTX-216, we treated NF1 loss-of-function melanoma cell lines with MTX-216, MTX-211 (the structural analogue of MTX-216 that has no effect on melanoma cells) as well as commericial kinase inhibitors, trametinib and pictilisib, and compared their gene expression profiles.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

42 Samples

Download data: CSV