Analysis of the oncolytic effect of ZIKV on temozolomide-resistant glioblastoma cells

• Grant number: 23/02209-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Oswaldo Keith Okamoto
• Grantee: Isabela Fonseca de Oliveira Granha
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID

Abstract

Glioblastoma (GBM) is an aggressive tumor that affects adult individuals. Because of this, the patient's median survival is estimated at just 15 months. Standard treatment consists of surgical resection followed by radiotherapy and chemotherapy with temozolomide (TMZ). Despite this, the tumor is highly recurrent. This pattern can be explained by the resistance GBM stem cells (GSC) acquire during the treatment, increasing tumor aggressiveness. Thus, new therapeutic alternatives are being explored. Among them, virotherapy, which consists of using genetically or non-genetically modified RNA or DNA viruses for the tumors treatment, has shown promising results. Within this perspective, the Zika virus (ZIKV), which has tropism for central nervous system, demonstrated oncolytic activity against several tumors located in this anatomical site, especially GBM. Interestingly, reviewing the literature, we observed that markers and pathways that contribute to the generation and maintenance of the TMZ resistance phenotype of GSC are also affected by ZIKV infection. More specifically, the Wnt/²-catenin, Hippo/YAP/TAZ pathways and SOX2, AXL and EZH2 markers are related to chemotherapy resistance and modulate ZIKV infection. Thus, we hypothesize that such targets interact to generate and increase resistance to TMZ and determine susceptibility to ZIKV infection. Furthermore, we believe TMZ-resistant cells may be more sensitive to ZIKV infection. Therefore we intend to investigate in the context of GBM strains with resistance to TMZ, the relationship of markers ²-catenin, YAP/TAZ, SOX2, AXL and EZH2 with the phenotype of resistance to chemotherapy and also with susceptibility to ZIKV infection . We emphasize that there are no published studies seeking to answer this question.

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)

FERREIRA, RODOLFO SANCHES; JANDREY, ELISA HELENA FARIAS; GRANHA, ISABELA; ENDO, ALICE KEI; FERREIRA, RAIANE OLIVEIRA; ARAUJO, BRUNO HENRIQUE SILVA; ZATZ, MAYANA; OKAMOTO, OSWALDO KEITH. Differential Replication and Oncolytic Effects of Zika Virus in Aggressive CNS Tumor Cells: Insights from Organoid and Tumoroid Models. Viruses-Basel, v. 16, n. 11, p. 14-pg., 2024-11-01. (19/27784-8, 23/02209-6, 20/14109-8, 21/04323-5, 13/08028-1)