isotretinoin + temozolomide + vorinostat

A combination therapy consisting of isotretinoin (a retinoid also known as cis-13-retinoic acid or cRA), temozolomide (an alkylating agent), and vorinostat (a histone deacetylase inhibitor also known as suberoylanilide hydroxamic acid or SAHA). This combination has been studied in clinical trials for the treatment of recurrent glioblastoma multiforme (GBM) and other malignant gliomas. Preclinical studies demonstrated that vorinostat can overcome resistance to isotretinoin and temozolomide in glioma models, leveraging potential synergistic effects. The combination leverages multiple mechanisms of action: vorinostat inhibits histone deacetylases leading to altered gene expression and enhanced access of DNA-targeted agents to chromatin; temozolomide causes DNA damage through alkylation, leading to cell death; and isotretinoin provides anti-tumor effects, with its efficacy potentially enhanced when combined with vorinostat. The rationale includes evidence that vorinostat can enhance the killing efficiency of various chemotherapeutic agents and increase radiation-induced cytotoxicity in glioblastoma cell lines.

Other names

Vorinostat, Isotretinoin, and Temozolomide combinationVorinostat + Isotretinoin + Temozolomide