Zika virus and brain cancer: Can Zika be an effective treatment for brain cancer? A systematic review

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// Mateus Gonçalves de Sena Barbosa 1 , Beatriz Rodrigues Messias 2 , Rafael Trindade Tatit 2 , Maycon Cristian Gomes de Paula 3 , Valdecir Boeno Spenazato Júnior 3 , Maria Gabriella Borges Braga 4 , Caio Vinícius Marcolino Santos 5 , 7 , Luiza D'Ottaviano Cobos 6 , 7 , Vinícius Otávio da Silva 1 , Eberval Gadelha Figueiredo 7 , Nicollas Nunes Rabelo 7 and Bipin Chaurasia 8 1 Department of Neurosurgery, Atenas University Center, Passos, Minas Gerais, Brazil 2 Hospital Israelita Albert Einstein, University of Israelita de Ciências da Saúde Albert Einstein, São Paulo, Brazil 3 Department of Neurosurgery, University of Sapucaí Valley, Pouso Alegre, Minas Gerais, Brazil 4 Department of Neurosurgery, Atenas University Center, Sete Lagoas, Minas Gerais, Brazil 5 Department of Neurosurgery, Nove de Julho University, Campus Vergueiro, São Paulo, Brazil 6 Department of Neurosurgery, José do Rosário Vellano University, Alfenas, Minas Gerais, Brazil 7 Division of Neurosurgery, School of Medicine-University of São Paulo (FMUSP), Hospital das Clínicas/FMUSP, São Paulo, Brazil 8 Department of Neurosurgery, Neurosurgery Clinic, Birgunj, Nepal Correspondence to: Bipin Chaurasia, email: trozexa@gmail.com , ORCID: orcid.org/0000-0002-8392-2072 Keywords: Zika; neurotropism; glioblastoma; glioma; brain tumor Received: June 21, 2024 Accepted: August 20, 2024 Published: September 30, 2024 Copyright: © 2024 de Sena Barbosa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Introduction: Many studies have highlighted the use of oncolytic viruses as a new class of therapeutic agents for central nervous system (CNS) tumors, especially glioblastomas (GMB). Zika Virus (ZIKV) proteins targeted to specific stem cells have been studied in vitro and animal models with promising results. Materials and Methods: A systematic review evaluated the efficacy and safety of the ZIKV use for CNS tumors treatment. Data were extracted and the in vivo studies were evaluated using the Robins-I tool. We assessed bias in each study using criteria such as selection bias, performance bias, detection bias, attrition bias, reporting bias, and others. According to Cochrane guidelines, bias was classified as high, low, or uncertain. High bias occurred when studies did not meet the criteria. Low bias was assigned when criteria were clearly met. Uncertain bias reflected insufficient information for a clear classification. Results: The 14 included studies shown that ZIKV reduced cell viability or inhibited the growth, proliferation of glioma stem cells (GSCs), and Bcl2 expression - which could potentially enhance the effect of chemotherapy/radiotherapy; caused cytopathic effects, induced tumor cell damage, manifested oncolytic properties, and even selectively safely killed GSCs; ultimately, it led to significant tumor remission and enhanced long-term survival through enhanced T-cell response. Conclusions: Although current evidence suggests ZIKV as a promising treatment for CNS tumors and may improve survival when combined with surgery and radiotherapy. Despite limited human evidence, it shows potential benefits. Further research is needed to confirm safety, efficacy, and optimize treatment in humans.

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