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I-SPY2-990 mRNA/RPPA Data Resource

ABSTRACT: The I-SPY2-990 mRNA/RPPA data resource contains gene expression, protein/phosphoprotein and clinical data for ~990 patients from the first 10 completed arms of the I-SPY 2 platform trial for aggressive, early stage breast cancer. Experimental treatments include pan-HER2 inhibitors and anti-HER2 agents, PARP inhibitor/DNA damaging agent combinations, an AKT inhibitor, immunotherapy, and ANG1/2, IGF1R and HSP90 inhibitors added to standard of care chemotherapy. All patients have pretreatment full transcriptome expression data on over ~19,000 genes assayed on Agilent 44K. 736 patients (all arms except ganitumab and ganetespib) have normalized LCM-RPPA data for 139 key signaling proteins/phosphoproteins in cancer. Clinical data includes HR, HER2 and MP status, response (pCR or no pCR), and treatment arm. This SuperSeries is composed of the mRNA and RPPA SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196096 | GEO | 2022/05/25

REPOSITORIES: GEO

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I-SPY2-990 mRNA/RPPA Data Resource: mRNA component

Project description:The I-SPY2-990 mRNA/RPPA Data Resource contains gene expression and clinical data for 987 patients from 10 arms of the neoadjuvant I-SPY2 TRIAL for aggressive early stage breast cancer [210 Control (Ctr); 71 veliparib/carboplatin (VC); 114 neratinib (N); 93 MK2206; 106 ganitumab; 93 ganetespib; 134 trebananib; 52 TDM1/pertuzumab(P); 44 H/P; 69 pembrolizumab (pembro)]. All 987 patients have pretreatment full transcriptome expression data on over ~19,000 genes assayed on Agilent 44K. Clinical data includes HR, HER2 and MP status, response (pCR or no pCR), and treatment arm. The ISPY2-990 mRNA/RPPA Data Resource also includes normalized pre-treatment LCM-RPPA data for 139 key signaling proteins/phosphoproteins in cancer for 736 patients (see companion GEO record GSE196093 for data and details).

2022-05-25 | GSE194040 | GEO

I-SPY2-990 mRNA/RPPA Data Resource: RPPA component

Project description:The RPPA component of the I-SPY2-990 mRNA/RPPA Data Resource contains protein/phosphoprotein data from pre-treatment laser capture microdissected (LCM) tumor biopsies for 139 key signaling proteins/phosphoproteins in cancer for 736 patients from 8 arms of the neoadjuvant I-SPY2 TRIAL (NCT01042379) for aggressive early stage breast cancer [194 Control (Ctr); 63 veliparib/carboplatin (VC); 105 neratinib (N); 87 MK2206; 128 trebananib; 49 TDM1/pertuzumab(P); 43 H/P; and 67 pembrolizumab (pembro)]. This record also contains clinical data for these patients, including HR, HER2 and MP status, response (pCR or no pCR), and treatment arm. RPPA endpoints assayed are from hormone receptor (n=4), HER family (n=14), cell cycle/proliferation (n=20), immune (n=18), DNA repair deficiency (DDR; n=15), AKT/mTOR/PI3K (n=7), apoptosis/autophagy (n=10), IGF1R (n=6), TIE/ANG (n=4), growth/survival/metabolism (n=22) and RTK (n=19) pathways. For gene expresson data for all 736 patients with RPPA data, plus an additional 150 patients for a total 987 patients from 10 arms of I-SPY2 (mRNA component of the I-SPY2-990 Data Resource), see the companion GEO record/subseries GSE194040.

2022-05-25 | GSE196093 | GEO

I-SPY2-990 mRNA/RPPA Data Resource: RPPA component

Project description:I-SPY2-990 mRNA/RPPA Data Resource: RPPA component

| PRJNA803248 | ENA

I-SPY2-990 mRNA/RPPA Data Resource

Project description:I-SPY2-990 mRNA/RPPA Data Resource

| PRJNA803240 | ENA

I-SPY2-990 mRNA/RPPA Data Resource: mRNA component

Project description:I-SPY2-990 mRNA/RPPA Data Resource: mRNA component

| PRJNA798787 | ENA

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2-positive breast cancer in the adaptively randomized I-SPY2 trial.

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2021-08-24 | GSE181574 | GEO

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 platform trial

Project description:Durvalumab with olaparib was one of the experimental regimens evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer, and graduated in the HER2- and HR+HER2- signatures. We hypothesized that (pre-treatment) expression-based immune signatures may predict response to the immune checkpoint inhibitor durvalumab and signatures related to DNA repair deficiency (DRD) may associate with response to olaparib. In this analysis, we assessed 13 expression based signatures related to immune, DRD, proliferation and estrogen signaling as specific predictor of pathologic complete response (pCR) to durvalumab/olaparib.

2021-06-10 | GSE173839 | GEO

AKT/mTOR/HER/PI3K family genes as predictors of pCR for early stage breast cancer patients treated with the AKT inhibitor MK2206 in the I-SPY 2 TRIAL (NCT01042379)

Project description:The AKT inhibitor MK2206 (M) was one of the experimental agents evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer, and graduated in the HER2+, HR-, and HR-HER2+ signatures. Based on the hypotheses that since MK2206 is an enzymatic inhibitor of AKT, response to MK2206 may be predicted by the relative pre-treatment levels of AKT kinase substrates, in pre-defined analyses we assessed 10 genes in the HER-AKT-mTOR pathway to test their association with pCR (complete pathologic response) in the MK2206 arm, in both HER2+ and HER2- subsets. We also tested 9 genes genes previously associated with response to MK2206 in vitro and in the HER2+ metastatic setting, and performed exploratory association analyses using whole-transcriptome data to identify additional predictive signals outside the HER-AKT-mTOR pathway.

2020-09-20 | GSE149322 | GEO

Ganitumab and Metformin plus Standard Neoadjuvant Therapy in Stage 2/3 Breast Cancer: Results from the I-SPY2 Adaptively Randomized Platform Trial

Project description:Ganitumab and Metformin was one of the experimental regiments evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer. Based on the hypotheses that pre-treatment IGF-1R axis signaling at the expression level may predict response to Ganitumab and Metformin, in pre-defined analyses we assessed 11 genes involved in IGF1R pathway signaling, the IGFBP5/IGFBP4 ratio, and two IGFR expression signatures to test their association with pCR (complete pathologic response).

2021-08-24 | GSE180962 | GEO

Expression data from wildtype and spy-3 roots

Project description:SPY is an O-linked N-acetylglucosamine transferase involved in many signaling and developmental processes in Arabidopsis. SPY also has a role in root development. In the spy mutant, a middle cortex is produced prematurely. To understand how SPY regulates root cortex proliferation, we sought to identify the genes affected by the spy mutation in the root.

2015-05-16 | GSE50952 | GEO

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