Ascites, High Grade Ovarian Serous Adenocarcinoma, Ovarian Cancer
Conditions
Brief summary
This project entails the collection of a prospective cohort of ascites (AS) samples from High Grade Serous Ovarian Cancer (HGSOC) patients. High Grade Serous Ovarian Cancer (HGSOC) is a major cause of cancer-related mortality, due to the late-stage diagnosis and failure of surgery and chemotherapy (CHT) to eradicate the disease with no significant improvement in overall survival. The primary objective of the project is to generate a comprehensive map of ascites cell components, detailing both their intrinsic features and the landscape of cellular interactions mediated by soluble factors in ascitic fluid.
Detailed description
HGSOC is a major cause of cancer-related mortality, due to the late-stage diagnosis and failure of surgery and chemotherapy (CHT) to eradicate the disease with no significant improvement in overall survival. In recent years, new therapeutic regimens are being tested to improve the care of HGSOC patients. These approaches include the use of poly-ADP-ribose polymerase inhibitors (PARPi) targeting Homology Directed Repair deficiency, anti-angiogenic drugs, such as anti-VEGF monoclonal antibodies, and immune checkpoint inhibitors, that target immune modulation induced by tumor and tumor-associated cells and inflammatory signals. Unfortunately, the outcome of such therapies has been to date either erratic or dismal. This points to the acute need to identify new biomarkers predictive of treatment response, effectively geared to the clinical setting. The primary objective of the project is to generate a comprehensive map of ascites cell components, detailing both their intrinsic features and the landscape of cellular interactions mediated by soluble factors in ascitic fluid. This will allow to define tumoral archetypes, reflecting HGSOC's endophenotypes, associated with prognosis in patients, possibly guiding future refined therapeutical paradigms for ovarian cancer patients and endowing researchers with a well-characterized multilayered dataset for future reference in the context of molecular dissection and target discovery paradigms. Indeed, the combination of origin- and archetype-based stratification of HGSOC patients, will allow to better identify patients for which existing therapeutical regimens could be beneficial, such as the use of checkpoint inhibitors and anti-angiogenic drugs, that have been so far erratic in ameliorating patient's survival.
Interventions
None listed
Sponsors
European Institute of Oncology
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Inclusion criteria
* Patients with suspicious or confirmed ovarian cancer pathology undergoing debulking surgery * Diagnosis of high grade serous ovarian cancer confirmed by histopathology assessment * Patients who provided written informed consent
Exclusion criteria
* HIV-positive patients * HBV-positive patients * HCV-positive patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Generation of a comprehensive map of ascites cell components | 48 month | The samples will be stratified according to a DNA-methylation based signature specific for the tissue of origin of HGSOC. The cellular fraction derived from ascites samples will be profiled by single cell multiomics to define the cell populations associated to either the fallopian tube or ovarian surface epithelium origin. In parallel, ascitic fluid will be profiled by ELISA to define the soluble components present in the two HGSOC subtypes. These data will be used to generate a map of ascites cell components and biomarkers specific for the two tissues of origin of this disease. This map will be exploited to highlight possible therapeutic avenues for HGSOC patients. |
Countries
Italy
Contacts
Primary ContactGiuseppe Testa
Backup ContactPietro Lo Riso
Outcome results
None listed