A Novel Liver Cancer-Selective Histone Deacetylase Inhibitor Is Effective against Hepatocellular Carcinoma and Induces Durable Responses with Immunotherapy.

ABSTRACT: Hepatocellular carcinoma (HCC) progression is facilitated by gene-silencing chromatin histone hypoacetylation due to histone deacetylase (HDAC) activation. However, inhibiting HDACs-an effective treatment for lymphomas-has shown limited success in solid tumors. We report the discovery of a class of HDAC inhibitors (HDACi) that demonstrates exquisite selective cytotoxicity against human HCC cells. The lead compound STR-V-53 (3) showed a favorable safety profile in mice and robustly suppressed tumor growth in orthotopic xenograft models of HCC. When combined with the anti-HCC drug sorafenib, STR-V-53, showed greater in vivo efficacy. Moreover, STR-V-53 combined with anti-PD1 therapy increased the CD8⁺ to regulatory T-cell (Treg) ratio and survival in an

SUBMITTER: Wu B 

PROVIDER: S-EPMC11475281 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature