Evaluation of a DNA demethylating agent in combination with all-trans retinoic acid for IDH1-mutant gliomas.

ABSTRACT:

Background

Isocitrate Dehydrogenase 1/2 (IDH1/2) mutations are diagnostic for Astrocytoma or Oligodendroglioma, IDH-mutant. In these IDH-mutant gliomas, retinoic acid-related gene expression is commonly silenced by DNA hypermethylation. DNA demethylating agents can epigenetically reprogram IDH-mutant cells and reduce proliferation, likely by re-expression of silenced tumor suppressor pathways. We hypothesized that DNA demethylation might restore the retinoic acid pathway and slow tumor growth. This was the rationale for a preclinical evaluation combining the DNA demethylating agent, 5-Azacytidine (5-Aza), and retinoic acid pathway activation with all-trans retinoic acid (atRA) in IDH-mutant glioma.

Methods

In this study, we evaluated the effect of 5-Aza and atRA combination

SUBMITTER: da Costa Rosa M 

PROVIDER: S-EPMC9071298 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature