Journal Article

Entinostat: a promising treatment option for patients with advanced breast cancer

Connolly, Roisin M, Piekarz, Richard, Rudek, Michelle A

2017

Overview

Entinostat is a synthetic benzamide derivative histone deacetylase (HDAC) inhibitor, which potently and selectively inhibits class I and IV HDAC enzymes. This action promotes histone hyperacetylation and transcriptional activation of specific genes, with subsequent inhibition of cell proliferation, terminal differentiation and apoptosis. This oral HDAC inhibitor has been evaluated in Phase I and II trials in patients with advanced malignancies, and is in general well tolerated. Entinostat does not currently have regulatory approval for clinical use; however promising preclinical and clinical data exist in hormone-resistant breast cancer. An ECOG-ACRIN Phase III registration study is ongoing in advanced breast cancer (E2112, NCT02115282) and aims to confirm the overall survival advantage observed with the combination of exemestane and entinostat/placebo in the Phase II setting (ENCORE301 trial). This article provides an overview of the chemistry, pharmacokinetics/pharmacodynamics and available clinical data for entinostat with a focus on advanced breast cancer.

• Publisher: Future Medicine Ltd
• Subject: Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Apoptosis / Apoptosis - drug effects / Benzamides - administration & dosage / Benzamides - adverse effects / Biomarkers / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - pathology / Cancer therapies / Cell Line, Tumor / Cell Proliferation - drug effects / clinical trials / Deoxyribonucleic acid / DNA / DNA methylation / Drug Evaluation / Drug-Related Side Effects and Adverse Reactions - classification / Drug-Related Side Effects and Adverse Reactions - pathology / Endocrine therapy / entinostat / Enzymes / Epigenesis, Genetic - genetics / Epigenetics / Estrogens / FDA approval / Female / Gene expression / histone deacetylase inhibitor / Histone Deacetylase Inhibitors - administration & dosage / Histone Deacetylase Inhibitors - adverse effects / Humans / Leukemia / Lung cancer / Metastasis / Neoplasm Staging / Pyridines - administration & dosage / Pyridines - adverse effects / Regulatory approval / Tumors / Womens health