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A Molecular Profile of Colorectal Cancer to Guide Therapy

ABSTRACT: A Molecular Profile of Colorectal Cancer to Guide Therapy

PROVIDER: PRJNA221862 | ENA |

REPOSITORIES: ENA

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A Molecular Profile of Colorectal Cancer to Guide Therapy [PDCCEs]

Project description:The ability to dissect heterogeneity in colorectal cancer (CRC) is a critical step in developing predictive biomarkers. The goal of this study was to develop a gene expression based molecular subgrouping model, which predicts the likelihood that patients will respond to specific therapies. Using microarray data compiled from 848 CRC patients, we developed a subgrouping model based on 23 activated oncogenic pathway expression signatures. Stability of the model was validated in two independent data sets. To test the capacity of our model to predict patient response to specific targeted therapies and to determine the sensitivity of the subgroups to chemotherapy in vivo, we treated patient-derived colorectal cancer explants (PDCCEs) predicted to have high mTOR pathway activity with everolimus or oxaliplatin. Results: A molecular profile of the discovery dataset revealed 8 molecular subgroups of colorectal cancer (MSCC). Both validation sets also exhibited 8 MSCC and demonstrated significant similarities to the discovery dataset. MSCC predicted to have active mTOR pathway signaling were more sensitive to everolimus compared to MSCC predicted to have low mTOR pathway activity (p=0.016). Furthermore, MSCCs displayed differential sensitivities to oxaliplatin (p<0.05). The ability to predict oncogenic signaling pathway activation is a powerful tool that may be used to sub-classify CRCs into clinically relevant MSCCs. Patterns of pathway activation may be used to target specific therapies in CRC patients and identification of sensitivities of MSCC to specific drugs can be a powerful approach to guide therapy for CRC patients.

2016-12-31 | GSE41568 | GEO

A Molecular Profile of Colorectal Cancer to Guide Therapy [HMEC]

Project description:Here we describe the generation and application of a gene expression signature for the Rheb pathway. Affymetrix array data obtained from human mammary epithelial cells over expressing Rheb or GFP were used to generate a Rheb/mTOR activation signature. To test the capacity of the signature to predict patient response to everolimus we treated patient-derived colorectal cancer explants (PDCCEs) predicted to have high and low Rheb pathway activity withthe mTOR inhibitor everolimus.

2016-12-31 | GSE51242 | GEO

A Molecular Profile of Colorectal Cancer to Guide Therapy

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-12-31 | GSE51244 | GEO

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Project description:A Molecular Profile of Colorectal Cancer to Guide Therapy [HMEC]

| PRJNA221801 | ENA

Homo sapiens

Project description:A Molecular Profile of Colorectal Cancer to Guide Therapy [PDCCEs]

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Multiomics analysis revealed proteomic subtyping of hepatocellular carcinoma guide the precise therapy of sorafenib

Project description:Multiomics analysis revealed proteomic subtyping of hepatocellular carcinoma guide the precise therapy of sorafenib

2023-10-30 | PXD046519 |

Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases can be used to guide therapy

Project description:Purpose: Colorectal cancer (CRC) patients with peritoneal metastases (CRPM) have limited treatment options and the lowest CRC survival rates. We aimed to determine whether organoid testing could help guide precision treatment for CRPM patients, as the clinical utility of prospective, functional drug screening including non-standard agents is unknown. Experimental Design: CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing. Results: Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for 2 patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications. Conclusions: Our approach is feasible, reproducible and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

2020-05-31 | GSE147971 | GEO

Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases can be used to guide therapy

Project description:Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases can be used to guide therapy

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Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases can be used to guide therapy

Project description:Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases can be used to guide therapy

| PRJNA622682 | ENA

Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases can be used to guide therapy

Project description:Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases can be used to guide therapy

| PRJNA629387 | ENA

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