Characterization o the RSK-independent mechanisms of BI-D1870 that potentiate the activity of therapeutic oncolytic viruses in glioblastoma cells

• Grant number: 17/50150-0
• Support type: Regular Research Grants
• Duration: March 01, 2018 - February 29, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Cooperation agreement: Consortium of Alberta, Laval, Dalhousie and Ottawa (CALDO)
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal researcher: Martín Roffé
• Grantee: Martín Roffé
• Principal researcher abroad: Tommi Alain
• Institution abroad: University of Ottawa (uOttawa), Canada
• Home Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated research grant: 15/15451-3 - Study on the Regulation and Function of the RSK Family in Glioblastomas, AP.R

Abstract

Brain tumours, particularly glioblastoma (G8M), have limited therapeutic options. New therapies are needed against this almost universally fatal cancer. In recent years, scientists have developed approaches that involve the use of common viruses to reactivate the immune system within patients to enable it to recognize and eliminate cancer cells. The laboratory of Dr. Alain at University of Ottawa, Canada, has experience working with the herpes simplex virus (HSV1) and the infection of various cancer cell types. Recently, they have identified a chemical anti-cancer agent, BI-D1870, that dramatically enhances the ability of the virus to propagate inside brain cancer cells but not inside normal cells. BI-D1870 was first described as an inhibitor of the p90 ribosomal S6 kinase family (RSK), however, different works, including Dr. Roffés, have demonstrated that BI-D1870 elicit off-target activities. These off-target effects seem to be responsible for the propagation of HSV1 in cancer cells and the aim of this proposal is to define those mechanisms. For that purpose, we will generate RSK-knockout G8M cells by using the CRISPR/Cas9 system, which will be essential to understand the RSK-independent effects of BI-D1870. This work will help to design more effective viral-mediated therapies to fight cancer. (AU)