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

• Grant number: 14/19171-2
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: September 01, 2015
• End date: August 31, 2019
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Paulo D'Amora
• Grantee: Paulo D'Amora
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Edson Guimarães Lo Turco ; Ismael Dale Cotrim Guerreiro da Silva ; Philip J. DiSaia ; Robert Alan Nagourney
• Associated scholarship(s): 17/24604-3 - Correlation between circulating steroid metabolites and clinical response parameters in patients with advanced Epithelial Ovarian Cancer: a metabolomic approach, BP.DD; 15/16921-3 - 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, BP.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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

D'AMORA, PAULO; SILVA, ISMAEL DALE C. G.; TEWARI, KRISHNANSU S.; BRISTOW, ROBERT E.; CAPPUCCINI, FABIO; EVANS, STEVEN S.; SALZGEBER, MARCIA B.; ADDIS-BERNARD, PAULA J.; PALMA, ANTON M.; MARCHIONI, DIRCE M. L.; et al. Platinum resistance in gynecologic malignancies: Response, disease free and overall survival are predicted by biochemical signature: A metabolomic analysis. GYNECOLOGIC ONCOLOGY, v. 163, n. 1, p. 162-170, OCT 2021. (14/19171-2, 15/16921-3)

D'AMORA, PAULO; COTRIM GUERREIRO SILVA, ISMAEL DALE; CASTRO, RODRIGO DE AQUINO; SALZGEBER, BATISTA MARCIA; BRISTOW, ROBERT; EVANS, STEVEN; DISAIA, PHILIP J.; ROBERT, ALAN NAGOURNEY. Metabolomic signatures in patients with advanced epithelial ovarian cancer: Correlation with clinical response parameters in a phase II study.. Clinical Cancer Research, v. 24, n. 1, p. 2-pg., 2018-01-01. (14/19171-2, 15/16921-3)