Entinostat for treatment of solid tumors and hematologic malignancies

A key feature of malignant cells is inappropriate gene suppression resulting in uncontrolled proliferation, continued cell cycling and a lack of differentiation. Histone deacetylase inhibitors (HDACi) are an emerging class of antineoplastic agents that counteract this effect and thus permit re-expression of silenced genes. Entinostat is an emerging HDACi that has shown promise in multiple preclinical studies. Additionally, Phase I and II clinical trials have begun to demonstrate its potential as a well-tolerated agent with anti-tumor activity.

The pharmacokinetics, pharmacodynamics, mechanisms of action, safety and tolerability, and clinical trials of entinostat are reviewed. Sources for this review included all relevant, publicly available, entinostat-related peer-reviewed publications and meeting abstracts up to March 2011.

Entinostat is a well-tolerated HDACi that demonstrates promising therapeutic potential in both solid and hematologic malignancies. Its efficacy does not appear directly dose-related, and as such, more relevant biomarkers are needed to adequately assess its activity. Future clinical trials will likely focus on its use in combination with other agents that are able to exploit the epigenetic changes rendered by deacetylase inhibition.