Molecular and functional landscape of malignant serous effusions for precision oncology
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PROVIDER: PRJNA1005925 | ENA |
REPOSITORIES: ENA
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Project description:Molecular and functional landscape of malignant serous effusions for precision oncology [MSE_drug_treated]
| PRJNA1005930 | ENA
Project description:Molecular and functional landscape of malignant serous effusions for precision oncology [MSE_baseline]
| PRJNA1005931 | ENA
Project description:Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells. These patients frequently develop malignant serous effusions (MSE). The value of MSE-based tumor cell characterization for guiding precision oncology is, however, currently unclear. Here, we present a comprehensive characterization of a pan-cancer cohort of 150 MSE samples at the cellular, molecular, and functional level. Our integrative analysis reveals dynamic cellular heterogeneity in MSE, and uncovers links between tumor driver mutations and ex vivo growth patterns. Strong concordance between genomic and transcriptional profiles of MSE and their corresponding solid tumors validates their use as a model system for solid tumor biology. We link baseline gene expression patterns to global ex vivo drug sensitivity, and demonstrate that drug-induced transcriptional changes in MSE are highly indicative of compound mode of action. Two case studies exemplify the utility of our approach in investigating acquired resistance to targeted therapy and identifying treatment options for relapsed solid tumors. In summary, our study provides a functional multi-omics view on a pan-cancer MSE cohort and underlines the utility of MSE-based precision oncology.
2024-08-26 | GSE240951 | GEO
Project description:Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells. These patients frequently develop malignant serous effusions (MSE). The value of MSE-based tumor cell characterization for guiding precision oncology is, however, currently unclear. Here, we present a comprehensive characterization of a pan-cancer cohort of 150 MSE samples at the cellular, molecular, and functional level. Our integrative analysis reveals dynamic cellular heterogeneity in MSE, and uncovers links between tumor driver mutations and ex vivo growth patterns. Strong concordance between genomic and transcriptional profiles of MSE and their corresponding solid tumors validates their use as a model system for solid tumor biology. We link baseline gene expression patterns to global ex vivo drug sensitivity, and demonstrate that drug-induced transcriptional changes in MSE are highly indicative of compound mode of action. Two case studies exemplify the utility of our approach in investigating acquired resistance to targeted therapy and identifying treatment options for relapsed solid tumors. In summary, our study provides a functional multi-omics view on a pan-cancer MSE cohort and underlines the utility of MSE-based precision oncology.
2024-08-26 | GSE240952 | GEO
Project description:Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional level. We find that MSE-derived cancer cells retain the genomic and transcriptomic profiles of their corresponding primary tumors, validating their use as a patient-relevant model system for solid tumor biology. Integrative analyses reveal that baseline gene expression patterns relate to global ex vivo drug sensitivity, while high-throughput drug-induced transcriptional changes in MSE samples are indicative of drug mode of action and acquired treatment resistance. A case study exemplifies the added value of multi-modal MSE profiling for patients who lack genetically stratified treatment options. In summary, our study provides a functional multi-omics view on a pan-cancer solid tumor cohort and underlines the feasibility and utility of MSE-based precision oncology.
2024-10-04 | PXD052582 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-08-26 | GSE240953 | GEO
Project description:The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art Taqman-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment (complete response - CR vs. other), and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS: log-rank p=0.0000 and PFS: log-rank p=0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions. In the study presented here, effusion samples were obtained from 32 patients diagnosed with serous ovarian carcinoma (n=25), primary peritoneal serous carcinoma (n=6) or tubal serous carcinoma (n=1). They were accrued at the Division of Pathology in the Norwegian Radium Hospital from 2000-2006. RNA was used to study the expression profile of 381 multidrug resistant-related genes.
2011-11-17 | E-GEOD-29702 | biostudies-arrayexpress
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
Project description:CPTAC: Microscaled Proteogenomic Methods for Precision Oncology
| PRJNA574688 | ENA
Project description:CPTAC: Microscaled Proteogenomic Methods for Precision Oncology
| PRJNA574689 | ENA