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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]

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 [PI3K panel]

PROVIDER: PRJNA632733 | ENA |

REPOSITORIES: ENA

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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]

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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.

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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

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.

2016-07-06 | GSE70018 | GEO

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

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

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

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

| PRJNA632732 | ENA

MK-2206 and AZD6244 in Patients With Advanced Colorectal Carcinoma

Project description:Background: - MK-2206 and AZD6244 (Selumetinib) are experimental cancer treatment drugs that block the effect of certain proteins that cancer cells need to grow and survive. These drugs may be effective treatments for some types of colorectal cancer that has not responded to or has relapsed after standard treatment. Researchers are interested in studying how MK-2206 and AZD6244 affect levels of certain proteins in colorectal cancer tumor, and how well the drugs work against cancer cells by examining cells from a tumor sample collected before the drugs are given and again after the drugs are given. Objectives: - To evaluate the safety and effectiveness of MK-2206 and AZD6244 in individuals with advanced colorectal carcinoma that has not responded to standard treatments. Eligibility: - Individuals at least 18 years of age who have been diagnosed with advanced colorectal carcinoma that has not responded to at least one type of standard chemotherapy. Design: * Participants will be screened with a physical examination, medical history, blood tests, and tumor imaging studies. * Participants will take MK-2206 and AZD6244 by mouth for 4-week cycles of treatment, with one dose of MK-2206 per week and one dose of AZD6244 every day. (If participants have negative side effects from the medications, the doses will be adjusted to a smaller dose). Participants will keep a diary to record doses and keep track of any side effects. * During treatment, participants will have regular visits to the clinical center, involving blood and urine tests, tumor biopsies, and other examinations to monitor the effects of treatment. Participants will have imaging studies every two cycles (8 weeks) to study the cancer’s response to the treatment. * Participants will continue to have cycles of treatment for as long as the treatment continues to be effective and the side effects are not severe enough to stop participation in the study....

| 2105135 | ecrin-mdr-crc

A Study of Dalotuzumab + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + Ridaforolimus Combination Therapies in Participants With Advanced Cancer (MK-0646-027)

Project description:This is an open-label, two-part study to evaluate the safety and tolerability of combination treatment with dalotuzumab + MK-2206, dalotuzumab + MK-0752, or dalotuzumab + ridaforolimus (MK-8669). Part 1 of the study will determine the dose-limiting toxicities (DLTs) observed after administration of each of the combinations at various doses and define the maximum tolerated dose (MTD) of each combination. Part 2 of the study will assess preliminary anti-tumor activity of these combinations (at MTD) in two groups of participants with selected tumor biomarkers: one group with metastatic or recurrent platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and one group with metastatic or recurrent colorectal cancer. The dalotuzumab + ridaforolimus and dalotuzumab + MK-2206 arms will be enriched with female platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer participants. The dalotuzumab + MK-0752 arm will be enriched with metastatic or recurrent wild-type kirsten rat sarcoma (KRAS) colorectal cancer participants. The primary hypothesis is that the DLTs observed in adult patients with locally advanced or metastatic solid tumors after administration of each of the MK-MK doublets will be dose-dependent to allow for definition of a MTD within each MK-MK doublet.

| 2098289 | ecrin-mdr-crc

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