Validation of predictive biomarkers of survival in temozolomide treatment in glioblastoma

• Grant number: 21/02918-1
• Support type: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2022
• Effective date (End): October 31, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal researcher: Rui Manuel Vieira Reis
• Grantee: Ideli Zanesco Fontes Baptista
• Home Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Glioblastoma (GBM) is one of the most common neoplasia of the central nervous system, is characterized as a highly aggressive and invasive tumor, is related to high mortality rates and a poor prognosis. Currently, the standard treatment of this disease consists of surgical removal of the tumor, followed by chemotherapy associated with the use of temozolomide (TMZ), a DNA alkylating agent. The patients' response to treatment with TMZ, however, is quite unpredictable. In a recent study, our group identified some potentially predictive biomarkers of their response. The aim of this study is validating some of these biomarkers, in a new series of patients with GBM treated with TMZ, and through in vitro studies. In a new series of 140 cases of GBM from the Barretos Cancer Hospital and the Hospital das Clínicas, FMUSP-Ribeirão Preto. The molecular profile will be studied through the NanoString platform. In glioblastoma cell lines with different responses to TMZ, the CDK7 gene will be repressed through CRISPR-Cas9, and the response to temozolomide of the parental and CDK7 silenced lines will be evaluated. This study will allow to statistically and biologically validate the role of CDK7 and other biomarkers as predictors of temozolomide in patients with glioblastomas. (AU)