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

ABSTRACT: AKT/mTOR/HER/PI3K family genes and phospho-proteins as predictors of pCR for early stage breast cancer patients treated with the AKT inhibitor MK2206 in the I-SPY 2 TRIAL

PROVIDER: PRJNA632842 | ENA |

REPOSITORIES: ENA

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AKT/mTOR/HER/PI3K family proteins and phospho-proteins 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 phosphorylation of AKT kinase substrates, in pre-defined analyses we assessed 26 well known proteins/phospho-proteins in the HER-AKT-mTOR pathway to test their association with pCR in the MK2206 arm, in both HER2+ and HER2- subsets. We specifically used laser capture microdissection (LCM)- enriched tumor epithelium cell isolates from the clinical biopsy specimens as the sample input for all protein pathway activation analysis, which has been shown to be critical in accurate measurement of ubiquitously expressed and activated signaling proteins. To the best of our knowledge, this work represents the first rigorous study of association between direct measurement of AKT pathway activation using phospho-protein activation levels and response to MK2206 performed in early stage breast cancer patients.

2020-09-20 | GSE150575 | 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

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

| PRJNA632851 | ENA

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: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)

| PRJNA629770 | ENA

Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

Project description:This phase II clinical trial studies how well Akt inhibitor MK2206 works in treating patients with relapsed lymphoma. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

| 2099453 | ecrin-mdr-crc

Akt Inhibitor MK2206 in Treating Patients With Advanced Gastric or Gastroesophageal Junction Cancer

Project description:This phase II clinical trial studies how well Akt inhibitor MK2206 works in treating patients with advanced gastric or gastroesophageal junction cancer. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

| 2099584 | ecrin-mdr-crc

Expression data from wildtype and spy-3 roots

2015-05-16 | GSE50952 | GEO

Akt inhibitor MK2206 prevents influenza A(H1N1)pdm09 virus infection in vitro

Project description:The influenza A(H1N1)pdm09 virus caused a global flu pandemic in 2009 and contributes to seasonal epidemics. Different treatment and prevention options for influenza have been developed and applied with limited success. Here we report that an Akt inhibitor MK2206 possesses potent antiviral activity against influenza A(H1N1)pdm09 virus in vitro. We showed that MK2206 blocks the entry of different A(H1N1)pdm09 strains into cells. Moreover, MK2206 prevented A(H1N1)pdm09-mediated activation of cellular signaling pathways and the development of cellular immune responses. Importantly, A(H1N1)pdm09 virus was unable to develop resistance to MK2206. Thus, MK2206 is a potent anti-influenza A(H1N1)pdm09 agent. Total RNA obtained from NCI-H1666 cells, which are non-small cell lung cancer cell line. NCI-H1666 cells were non- or MK2206-treated (10 μM) and mock- or virus-infected (A/Helsinki/p14/2009) at moi of 3.

2014-01-23 | E-GEOD-54293 | biostudies-arrayexpress

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. The transciptomes from the root of one-week-old seedlings, Col or spy-3 mutant, were compared. The seedlings were grown on a nylon membrane placed on 1X MS agar medium and the plates are positionally vertically in a Pecival growth chamber with 16 hr light and 8 hr dark. Three biological replicates were performed.

2015-05-16 | E-GEOD-50952 | biostudies-arrayexpress

Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

Project description:This phase II trial studies how well v-akt murine thymoma viral oncogene homolog 1 (Akt) inhibitor MK2206 works in treating patients with previously treated colon or rectal cancer that has spread from the primary site to other places in the body or nearby tissue or lymph nodes and cannot be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

| 2140889 | ecrin-mdr-crc

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