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Evaluation of inhibition of therapeutic targets in Pancreatic Ductal Adenocarcinoma (PDAC) using three-dimensional tissue-specific models.

Grant number: 24/15154-8
Support Opportunities:Scholarships in Brazil - Master
Start date: October 01, 2024
End date: September 30, 2026
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Pedro Luiz Porfirio Xavier
Grantee:Beatriz Magalhães Gomes
Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
Associated research grant:22/06305-7 - Identifying new therapeutic targets in Pancreatic Ductal Adenocarcinoma by combining relevant models and approaches, AP.GR

Abstract

3D models that faithfully mimic in vivo tumor biology and improve our understanding of therapeutic responses are challenging but urgent to improve target discovery for PDAC. Cell culture models using tissue-specific ECM components have the ability to maintain transcriptional profiles, cancer stem cell (CSC) properties, and tumorigenicity. In this plan of activity, a Masters' student will evaluate the small-molecule inhibitors selected in the Scientific and Technical Challenge 1, in 3D tissue-specific environments for PDAC cells, in order to observe and further understand the effects of the therapeutic target inhibition on PDAC. Effects will be observed regarding growth, cell viability, cell death, and cell cycle of the spheroids. The student will also establish appropriate protocols to isolate and digest spheroids from the hydrogel beyond establishing suitable protocols to embed spheroids in paraffin and perform cryosection. These steps will be essential for transcriptomic analysis, in vivo assays, and histological, and immunohistochemical procedures. At the end of this project, we will further evaluate and characterize the effects of the therapeutic target inhibition in a faithful model, determining a new therapeutic target for PDAC.

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