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SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3-BASED GLIOMA PATIENT STRATIFICATION AND APPLICATION IN PRECISION ONCOLOGY

ABSTRACT: SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3-BASED GLIOMA PATIENT STRATIFICATION AND APPLICATION IN PRECISION ONCOLOGY

PROVIDER: PRJNA483546 | ENA |

REPOSITORIES: ENA

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SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3-BASED GLIOMA PATIENT STRATIFICATION AND APPLICATION IN PRECISION ONCOLOGY

Project description:Intratumoral heterogeneity is a hallmark of glioblastoma (GBM) tumors, thought to negatively influence therapeutic outcome. Previous studies showed that mesenchymal tumors fare more poorly than the proneural subtype. We focused on STAT3 because its activation precedes the proneural-mesenchymal transition. We first established a STAT3 gene signature that stratifies GBM patients into STAT3-high and -low cohorts. STAT3 inhibitor treatment selectively mitigated STAT3-high cell viability and tumorigenicity in orthotopic mouse xenograft models. Additionally, we defined the mechanism underlying resistance in STAT3-low cells by combining STAT3 signature analysis with kinome screen data on STAT3 inhibitor-treated cells. This allows us to draw connections between kinases affected by STAT3 inhibitors, their associated transcription factors and target genes. We demonstrate that dual inhibition of IGF-1R and STAT3 sensitized STAT3-low cells and improved survival in mice. Our study underscores the importance of serially profiling tumors so as to accurately target individuals who may demonstrate molecular subtype switching

2019-06-20 | GSE117905 | GEO

A Single-Cell Tumor Immune Atlas for Precision Oncology

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2020-10-27 | GSE158803 | GEO

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Project description:Patient-derived xenografts (PDX) and organoids (PDO) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of Micro- Organospheres (MOS) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of newly diagnosed metastatic colorectal cancer (CRC) patients using a MOS-based precision oncology pipeline reliably predicted patient treatment outcome within 14 days, a timeline suitable for guiding treatment decisions in clinic. Furthermore, MOS capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors.

2022-09-01 | GSE184242 | GEO

Genome-wide binding signature of Signal transducer and activator of transcription (STAT) family in colorectal cancer HCT 116 cell

Project description:The excessive and continuous activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway leads to the proliferation and migration of malignant cells resulting in the occurrence and development of almost all of cancers. The defined gene sets specifically activated by different STAT proteins are relied on their genomic accessibility by the interplay of certain STAT proteins with other potential cofactors. However, we have no clue about the status of human activated STAT dimers in the nucleus, as well as the intercrossing modules of synergic, supplementary or competitive relationship among each other in colorectal cancer. In current study, chromatin immunoprecipitation sequencing (ChIP-seq) was conducted to explore the genome-scale binding signatures of STAT1, STAT2, STAT3, STAT5A/B and STAT6 in human HCT-116 CRC cells. Moreover, STAT3 binding on genomic DNA was also investigated in HCT116 cells with NR5A2 knockdown.

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CPTAC: Microscaled Proteogenomic Methods for Precision Oncology

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CPTAC: Microscaled Proteogenomic Methods for Precision Oncology

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2021-02-11 | GSE166449 | GEO

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