A tumor-stroma PDAC model to evaluate the therapeutic effects of KRAS inhibitors

• Grant number: 24/09114-3
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: September 23, 2024
• End date: December 22, 2024
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Pedro Luiz Porfirio Xavier
• Grantee: Ana Júlia dos Santos Bianco Duarte
• Supervisor: Daniel Ohlund
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Institution abroad: Umeå University, Sweden
• Associated to the scholarship: 24/00635-0 - Establishment and characterization of a 3D tissue-specific platform for Pancreatic Ductal Adenocarcinoma cells, BP.IC

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer, with one of the poorest outcomes of all cancer, due to nonspecific symptoms, late diagnosis, and lack of effective therapeutic strategies. Recently, chemical inhibitors have been successfully developed to target KRAS, an important and well-known mutated gene and an oncogenic event of PDAC. Using these inhibitors in an in vitro co-culture model mixing Pancreatic Stellate Cells (PSCs) and PDAC organoids, which recapitulate tumor stroma and explore potential druggable targets, could significantly replicate the drug response of PDAC to KRAS inhibitors. Thus, this internship aims to properly learn how to handle, establish, and characterize in vitro co-culture models mixing PSCs and murine PDAC organoids. In addition, the student will evaluate the effects of KRASG12D inhibitors, such as MRTX1133 and BI-2865, and observe the therapeutic effects in this co-culture model.