vorinostat

Overview

Vorinostat (SAHA) is a pan-HDAC inhibitor with FDA approval for cutaneous T cell lymphoma. It is under investigation in solid tumors based on epigenetic vulnerabilities identified in specific molecular subtypes.

Evidence in the corpus

• Vorinostat showed selective efficacy against MG4 (proliferative) meningiomas in vitro and in vivo (patient-derived cell lines and xenografts), while having no effect on MG1–3 cell lines; this selectivity supports development of an MG4-targeted HDAC inhibitor trial for a cancer type with no effective medical therapies PMID:34433969.
• MG4 meningiomas are characterized by high proliferation, aggressive recurrence, and distinct multi-omic features (proteomics, methylation, mRNA) that underpin their vorinostat sensitivity; molecular classification is prerequisite for trial enrollment PMID:34433969.
• HDAC inhibition with vorinostat (NCT01075113) cited as a candidate targeted therapy for HCC in the context of 31 actionable alterations identified by ESCC/HCC genomic profiling PMID:24735922

Resistance mechanisms

• MG1–3 meningioma cell lines were resistant to vorinostat in the same in vitro system, indicating the efficacy is subtype-specific and limited to the proliferative MG4 group PMID:34433969.

Cancer types (linked)

• MNG

Sources

• PMID:34433969

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