Organoids Derived from Serous Ovarian Carcinomas: A Useful Model for Therapeutic Decisions.

• Grant number: 24/04461-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2025
• End date: November 30, 2027
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Silvia Regina Rogatto
• Grantee: Luiza Cortes
• Host Institution: Hospital das Clínicas da Faculdade de Medicina de Botucatu. Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Background: Ovarian cancer (OC) is the most lethal among gynecological cancers. Among the epithelial OC, which is the most prevalent, the high-grade serous ovarian carcinoma subtype is the most incident and aggressive. Initial treatment involves cytoreductive surgery and platinum-based chemotherapy, in which patients are initially responsive. The asymptomatic nature of OC leads to advanced diagnosis in 70% of cases, with only 25% surviving for 5 years (stage IIIC-IV). Over 30% of patients in advanced stages have malignant effusions at diagnosis, which are associated with recurrence and metastasis. Previous evidence from our group and the literature indicates that tumor-derived organoids (TDOs) are representative and recapitulate the original tumors regarding pathological and molecular features; therefore, they are an ideal model for advancing precision medicine. Objective: To molecularly characterize organoids derived from malignant effusions of patients with serous OC to identify patient-specific biomarkers and treatment targets. Patients and Methods: Thirty samples of malignant effusions were drained as part of the clinical routine of patients with serous OC (set 1) and 15 new cases will be collected. Isolated cells will be cultured in a 3D environment, and TDOs will be used for RNA extraction and sequencing. Data analysis and identification of differentially expressed genes will follow established pipelines and compared with public datasets. A better understanding of the molecular mechanisms influencing treatment response may lead to the discovery of new biomarkers and treatment targets that can increase survival with quality of life (thus avoiding toxicity from ineffective drugs) in ovarian cancer patients.