Identification of biomarkers predictive of response to temozolomide treatment in glioblastoma

• Grant number: 18/10511-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2018
• End date: April 30, 2020
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Rui Manuel Vieira Reis
• Grantee: Isabella Gomes
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Glioblastoma (GBM) is a highly aggressive and invasive tumor that confers high mortality rates and low survival. The standard treatment consists of surgical resection of the tumor, accompanied by radiotherapy and chemotherapy associated with the use of temozolomide (TMZ), a DNA alkylating agent that, administered to the patient, promotes a slight increase in survival. However, GBM presents intrinsic characteristics that confer chemoresistance to conventional treatment, making the search for new therapies necessary. In this sense, the investigation of biomarkers becomes promising, in an attempt to identify new therapeutic targets. Although the diagnosis of gliomas is performed by histopathological examination, recent advances have indicated the importance of molecular subtypes that may help to understand GBM heterogeneity and improve treatment. The objectives of this study are to identify the genetic profile of response to temozolamide in patients with glioblastoma. Evaluate nanostring expression of panel genes involved in DNA damage and repair pathways in GBM patients treated with TMZ (good response and poor response). Carry out the molecular profile (MGMT methylation, IDH1 / 2 and TERT mutations, ATRX expression and codeletion of 1p and 19q); and to correlate the genetic profile with molecular profile and response to treatment with temozolomide, trying to identify predictive biomarkers in noninvasive tests.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GOMES, ISABELLA; MORENO, DANIEL ANTUNES; DOS REIS, MARIANA BISARRO; DA SILVA, LUCIANE SUSSUCHI; LEAL, LETICIA FERRO; GONCALVES, GISELE MELO; PEREIRA, CAIO AUGUSTO; OLIVEIRA, MARCO ANTONIO; MATSUSHITA, MARCUS DE MEDEIROS; REIS, RUI MANUEL. Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide. JOURNAL OF NEURO-ONCOLOGY, v. 151, n. 2, JAN 2021. (18/10511-6)

MORENO, DANIEL ANTUNES; DA SILVA, LUCIANE SUSSUCHI; GOMES, ISABELLA; LEAL, LETICIA FERRO; BERARDINELLI, GUSTAVO NORIZ; GONCALVES, GISELE MELO; PEREIRA, CAIO AUGUSTO; SANTANA, IARA VIANA VIDIGAL; MATSUSHITA, MARCUS DE MEDEIROS; BHAT, KRISHNA; et al. Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients' survival. THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, v. 14, p. 15-pg., 2022-01-01. (18/10511-6)