Functional Validation of Therapeutic Targets in Patient-Derived Pancreatic Ductal Adenocarcinoma Organoids

• Grant number: 25/13426-3
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: February 02, 2026
• End date: August 01, 2026
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Pedro Luiz Porfirio Xavier
• Grantee: Beatriz Magalhães Gomes
• Supervisor: Tracy Putoczki
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Institution abroad: Walter And Eliza Hall Institute Of Medical Research, Australia
• Associated to the scholarship: 24/15154-8 - Evaluation of inhibition of therapeutic targets in Pancreatic Ductal Adenocarcinoma (PDAC) using three-dimensional tissue-specific models., BP.MS

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, exhibiting a 5-year survival rate lower than 10%, primarily due to challenges such as late-stage diagnosis, the absence of early clinical symptoms, a highly complex and heterogeneous pathophysiology, and the limited efficacy of current therapeutic approaches. These factors contribute to its poor prognosis, highlighting the urgent need for the development and validation of novel and more effective therapeutic strategies to combat PDAC. Organoids are three-dimensional cell culture models that preserve the tumor heterogeneity and architecture, recapitulating cancer response to therapies. This makes this model a robust platform to test and validate novel therapeutic approaches against cancer. This BEPE project aims to screen promising small-molecule inhibitors of a range of targets, such as kinases, mitochondrial complex I, epigenetic proteins, and growth factor receptors, on patient-derived organoids (PDOs) using a co-culture system with cancer-associated fibroblasts (CAFs), to mimic the response of the in vivo tumor. To achieve this objective, dose-response assays will be performed to further determine the IC50 of the compounds on PDOs co-cultured with CAFs, followed by the characterization of cell death mechanisms induced by the action of the inhibitors. For cell death characterization, fluorescence assays for apoptosis, necrosis, ferroptosis, and RT-qPCR for genes related to cupoptosis will be performed. The findings obtained in this project will be of great importance to fulfill the further objective of developing new targeted therapies against PDAC.