GQIcombi application to subdue glioma via differentiation therapy

Front Oncol. 2024 Jun 26:14:1322795. doi: 10.3389/fonc.2024.1322795. eCollection 2024.

Abstract

Current therapy protocols fail to cure high-grade gliomas and prevent recurrence. Therefore, novel approaches need to be developed. A re-programing of glioma cell fate is an alternative attractive way to stop tumor growth. The two-step protocol applies the antiproliferative GQ bi-(AID-1-T) and small molecule inducers with BDNF to trigger neural differentiation into terminally differentiated cells, and it is very effective on GB cell cultures. This original approach is a successful example of the "differentiation therapy". To demonstrate a versatility of this approach, in this publication we have extended a palette of cell cultures to gliomas of II, III and IV Grades, and proved an applicability of that version of differential therapy for a variety of tumor cells. We have justified a sequential mode of adding of GQIcombi components to the glioma cells. We have shown a significant retardation of tumor growth after a direct injection of GQIcombi into the tumor in rat brain, model 101/8. Thus, the proposed strategy of influencing on cancer cell growth is applicable to be further translated for therapy use.

Keywords: G-quadruplex oligonucleotides; antiproliferative activity; cancer stem cells; differentiation therapy; glioma; small molecule inducers.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Ministry of Science and Higher Education of the Russian Federation, grant number 075–15-2024–561.