Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Akt inhibition with MK-2206 is associated with favorable immune profile changes within the tumor microenvironment of hormone receptor positive, HER2 negative breast cancer

ABSTRACT: Akt inhibition with MK-2206 is associated with favorable immune profile changes within the tumor microenvironment of hormone receptor positive, HER2 negative breast cancer

PROVIDER: PRJNA632732 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Akt inhibition with MK-2206 is associated with favorable immune profile changes within the tumor microenvironment of hormone receptor positive, HER2 negative breast cancer [PI3K panel]

Project description:Gene expression was assessed with Nanostring in the surgical specimens obtained from a Window of Opportunity trial with MK-2206 in early stage breast cancer. Tumor biopsies and surgical specimens were compared for patients who received MK-2206 along with a prospective untreated control group of patients. Greater expression of interferon related genes was seen in surgical specimens following MK-2206 and compared to untreated controls.

2020-05-25 | GSE150509 | GEO

Akt inhibition with MK-2206 is associated with favorable immune profile changes within the tumor microenvironment of hormone receptor positive, HER2 negative breast cancer [IO360 panel]

2020-05-25 | GSE150458 | GEO

Selective Akt inhibition by MK-2206 eleminates colorectal cancer-initiating stem cells

Project description:To identify the regulatory mechanisms and signalling pathways involved in colorectal cancer (CRC) development, we compared the transcriptome of patient-derived tumor-initiating cells (TICs) with their normal stem cell counterparts of the same patient. This study demonstrates the relevance of AKT-signalling in colonic TIC proliferation and survival. Functional testing uncovered the selective AKT-inhibitor MK-2206 as a potential therapeutic for TIC-directed therapy in CRC. Gene expression profiling of tumor and normal tissues from 5 patients.

2016-07-06 | E-GEOD-70018 | biostudies-arrayexpress

Selective Akt inhibition by MK-2206 eleminates colorectal cancer-initiating stem cells

2016-07-06 | GSE70018 | GEO

A phase 1b study of the Akt-inhibitor MK-2206 in combination with weekly paclitaxel and trastuzumab in patients with advanced HER2-overexpressing solid tumor malignancies

Project description:16 patients with HER2+ tumors were enrolled (12 breast, 3 gastric, 1 esophageal). 27 samples (12 primary + 15 metastatic) from the 16 unique patients were assayed on Agilent 60K expression microarrays, and association between expression and response data were evaluated to identify potential biomarker of MK2206 response We conducted a phase 1b study of MK-2206 in combination with weekly paclitaxel 80 mg/m2 and trastuzumab 2 mg/kg in patients with HER2+ malignancies. Dose escalation was performed using a modified toxicity probability interval method. Molecular profiling of archived tissue samples and limited PK analyses were performed.

2016-07-31 | E-GEOD-75087 | biostudies-arrayexpress

Spatial proteomics of selinexor, MK-2206 and combination response in AML cells

Project description:In order to characterize the dynamics of proteins between different cellular compartments in response to selinexor (XPO1 inhibitor), MK-2206 (Akt inhibitor) an the combination i AML cells, we treated MV4-11 and PL-21 cells for 6 hours with DMSO, 1 uM selinexor, 1 uM MK-2206 or the combination. Each condition was performed in 4 biological bio-reps.

2022-08-07 | PXD033527 | Pride

Akt inhibition with MK-2206 is associated with favorable immune profile changes within the tumor microenvironment of hormone receptor positive, HER2 negative breast cancer [IO360 panel]

Project description:Akt inhibition with MK-2206 is associated with favorable immune profile changes within the tumor microenvironment of hormone receptor positive, HER2 negative breast cancer [IO360 panel]

| PRJNA632489 | ENA

Akt inhibition with MK-2206 is associated with favorable immune profile changes within the tumor microenvironment of hormone receptor positive, HER2 negative breast cancer [PI3K panel]

| PRJNA632733 | ENA

Endoxifen Downregulates AKT Phosphorylation Through Protein Kinase C Beta 1 in ER+/HER2- Breast Cancer

Project description:In phase I/II clinical trials, Z-endoxifen demonstrated substantial oral bioavailability and promising antitumor activity in endocrine-refractory estrogen-receptor positive breast cancer (ER+ BC) and other solid tumors, with plasma concentrations reportedly as high as 5 ï�M. Therefore, we explored the potential mechanisms of Z-endoxifen antitumor activity that extends beyond ERÎ± inhibition. In estrogen unstimulated aromatase-expressing ER+/human epidermal growth factor 2 receptor negative (HER2-) MCF7AC1 BC cells, Z-endoxifen at 5 ï�M, but not ERï�¡-targeting 0.01 and 0.1 ï�M concentrations inhibited growth and induced apoptosis, suggesting an ERÎ±-independent effect. Utilizing an unbiased mass spectrometry approach, we explored Z-endoxifen effects on other signaling pathways. Z-endoxifen at 5 ÂµM profoundly altered the phosphoproteome with minimal impact on total proteome. Computational analysis revealed Protein kinase C beta (PKCï�¢) and AKT1 as the prevalent upstream kinases for Z-endoxifen-downregulated protein phosphorylations. Notably, in ER+/HER2- BC models, Z-endoxifen at 5 ï�M attenuated AKTSer473 and AKT substrates in vitro in the presence of insulin and PKC agonist PMA and in vivo. Further, Z-endoxifen inhibited PKCï�¢1 kinase activity compared to other PKC isoforms in vitro and bound to PKCÎ²1. While PMA stimulated PKCï�¢1Ser661 phosphorylation correlated with AKTSer473 and AKT substrate phosphorylation, Z-endoxifen at 5 ï�M uniquely blocked these effects and induced PKCÎ²1 protein degradation. siRNA-mediated PKCï�¢1 knockdown attenuated AKTSer473 phosphorylation, suggesting PKCÎ²1-mediated suppression of AKT signaling by Z-endoxifen. Further, Z-endoxifen at 5 ï�M replicates the pan-AKT inhibitor MK-2206 effects on apoptosis. These findings implicate PKCÎ²1 as a novel Z-endoxifen substrate responsible for suppressing AKT signaling and inducing apoptosis in breast cancer.

2024-01-26 | PXD035007 | Pride

FOXO3a Is A Major Target Of Inactivation By PI3K/AKT Signaling In Aggressive Neuroblastoma

Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. Affymetrix U133 Plus 2.0 profiling of SY5Y-TetR-FOXO3A cells treated with doxycycline and/or the PI3K/mTOR inhibitor PI-103. Each condition profiled in triplicate.

2013-05-01 | E-GEOD-42762 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data