Characterization of novel drivers in the development of malignant neoplasias

• Grant number: 21/14253-4
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2022 - April 30, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Lucas Tadeu Bidinotto
• Grantee: Lucas Tadeu Bidinotto
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated researchers: Adhemar Longatto Filho ; Gustavo Ramos Teixeira ; Letícia Ferro Leal ; Renato José da Silva Oliveira ; Rui Manuel Vieira Reis ; Silvia Aparecida Teixeira

Abstract

Despite constant advances in cancer treatment, some tumor types continue to have very low morbidity and mortality. The Cancer Genome Atlas (TCGA) consortium has contributed to the identification of genomic and genetic alterations in several tumors. The extensive scientific production resulting from this program has, in general, found tumor subtypes that may be more (or less) resistant to treatment, with different survival (overall or disease-free survival), among others. However, there is information that has not yet been explored, mainly in the search for novel molecular markers for the development, progression or treatment of cancer. Thus, we aim to identify and characterize novel drivers in the development of cancer, with integrated approaches in silico, in vitro and in vivo. The first step will be a pan-cancer analysis of 33 TCGA datasets to identify potentially important genes in oncogenesis. These will then be silenced in vitro using CRISPR. The molecular pathways which these genes are involved will be analyzed through NanoString and the silenced strains will be functionally analyzed for proliferation, apoptosis, migration and invasion. Finally, the role of these genes of interest will be evaluated in vivo through the analysis of angiogenesis in the chorioallantoic membrane (CAM) and in xenografts in nude mice. Thus, we aim to find drivers that are still poorly explored in oncogenesis and characterize the pathways in which they participate, thus finding new targets for oncogenesis modulation. (AU)