DPF3 Impact on Renal Cancer: from susceptibility to murine treatment with immunotherapy

• Grant number: 21/14853-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): February 01, 2022
• Effective date (End): January 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Leandro Machado Colli
• Grantee: Leticia Andrade Costa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 20/10960-5 - Renal cancer genetic susceptibility, AP.JP

Abstract

Cancer is one of the most common causes of death in the world. Renal Carcinoma (RCC) is one of the ten main frequent types of Cancer, with an increasing number of new cases. Clear Cell Renal Carcinoma (ccRCC) is the most frequent subtype, responsible for about 75% of the cases. GWAS (Genome-Wide Association Study) is used for germline susceptibility discovery and has identified 13 regions for RCC. The SNP rs4903064, tag SNP for the 14q24 RCC region, is associated with increased expression of the DPF3 gene, which is a BAF SWI/SNF complex gene. In vitro, DPF3 overexpression increased cell growth rates and altered chromatin accessibility and gene expression, favoring oncogenic pathways. However, no study evaluated the DPF3 effect on in vivo models. Here, we aimed to evaluate the effects of DPF3 overexpression on tumor development and its relationship with immunotherapy. For this, we will use three models: 1) a xenotransplant model with human RCC cells that overexpress DPF3 to evaluate tumor progression and metastasis dissemination; 2) a model with RENCA cell that overexpresses DPF3 to evaluate the impact of DPF3 overexpression as a biomarker of immunotherapy treatment; 3) a transgenic model with conditional knockout of Vhl which also overexpress DPF3 to evaluate the impact of DPF3 on RCC development. The study will be critical for better understanding RCC development via DPF3 overexpression and its role in Renal Cancer immunotherapy, which can impact clinical care as a biomarker and new drug development. (AU)