Correlation between circulating steroid metabolites and clinical response parameters in patients with advanced Epithelial Ovarian Cancer: a metabolomic approach

• Grant number: 17/24604-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): December 01, 2017
• Effective date (End): July 31, 2019
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Paulo D'Amora
• Grantee: Márcia Batista Salzgeber
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 14/19171-2 - A study to correlate the activity of first-line chemotherapy with response, time to progression and overall survival in patients with advanced epithelial ovarian cancer, AP.JP

Abstract

Personalized Oncology has advanced through genomic & proteomic platforms. BCR-abl; EGFr & ALK have provided drug-able targets & companion diagnostics in several diseases, yet many transforming events in humans are polygenic, complex & incompletely understood at a genomic level. Recognition that oncogenesis reflects changes in the cell and its environment has renewed interest in whole cell experimental models that capture native-state cell-cell, -stroma & -vascular signaling. Ex vivo analysis of programmed cell death (EVA-PCD) as well as metabolomic analysis have been shown to correlate significantly with response, time to progression & survival in malignant disorders. Aims: we will study the correlation between the functional ex vivo analysis (EVA-PCD) with circulating lipid profiles using mass spectrometry, using a metabolomic approach, in patients with Advanced Epithelial Ovarian Cancer. Methods: a study protocol with 50 patients with advanced epithelial ovarian cancer undergoing surgical treatment and first line chemotherapy will be conducted at the Gynecologic Oncology Division of the University of California Irvine (UC, Irvine - California, USA). The ovarian tumor tissue will be submitted to dose-response curves using metabolic (ATP-content, mitochondrial) & morphologic endpoints (the Ex Vivo Analysis of Programmed Cell Death - EVA-PCD®). Mass spectrometry will analyze the same tumor tissue and peripheral blood of all patients for lipid profile detection at the Molecular Gynecology and Metabolomics Laboratory at the School of Medicine of the Federal University of São Paulo (EPM-UNIFESP - São Paulo, Brazil). Expected results: to identify correlation between EVA-PCD® functional testing and tissue/circulating lipid profiles with objective clinical response parameters: Complete Response (CR), Partial Response (PR), Time to Progression (TP) and Overall Survival (OS) in patients with Advanced Ovarian Epithelial Cancer. (AU)