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Research therapeutic targets from gene expression networks of members of the TGF-b pathway associated with tumor progression of ependymomas of worse prognosis

Grant number: 16/19799-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2017
Status:Discontinued
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Luiz Gonzaga Tone
Grantee:Keteryne Rodrigues da Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/20341-0 - Interactions between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on pediatric malignancies, AP.TEM
Associated scholarship(s):18/25924-4 - Understanding treatment resistance and evaluating new therapies for pediatric ependymoma, BE.EP.DR

Abstract

The ependymoma (EPN) is the third most frequently brain tumor in childhood, affecting intracranial region in 90% of cases. The treatment used today includes resection of the tumors followed by radiation, however even after treatment, a lot of patients will die because of resistance to therapy and tumor recurrence. The EPN is a heterogeneous disease, which the worst predictions are represented by molecular subgroups EPN-RELA and PF-EPN-A the latter being characterized, among other changes, by the overexpression of genes associated with the pathway of TGF-b signaling. The route of TGF-b signaling is involved in the processes of proliferation, differentiation, cell adhesion and migration, also acting on angiogenesis and apoptosis processes. This route can act either as tumor suppressor as promoter, depending on the cell type and its microenvironment. Some studies have shown that components of the TGF-b pathway are changed in ependymoma, but no study so far has shown the possible effects of the activity of this pathway in EPN biology, as well as the consequences of its modulation targets in the tumor progression of this cancer. The use of genomic methods of high performance and computational approaches newer makes possible the analysis of complex molecular interactions, modeling them as interaction networks favoring discovery of more specific molecular targets for use in the therapy of tumors with the worst prognosis ependimários. This work aims to identify transcriptional modules involved in the pathway TGF-b and study the role of these genes in EPN biology for the identification of potential therapeutic targets that can be used in the treatment of this cancer. (AU)