1. Entinostat: a promising treatment option for patients with advanced breast cancer
- Author
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Roisin M. Connolly, Richard Piekarz, and Michelle A. Rudek
- Subjects
0301 basic medicine ,Cancer Research ,Drug-Related Side Effects and Adverse Reactions ,Pyridines ,medicine.drug_class ,Apoptosis ,Breast Neoplasms ,Pharmacology ,Epigenesis, Genetic ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Exemestane ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Cell Proliferation ,Neoplasm Staging ,business.industry ,Entinostat ,Histone deacetylase inhibitor ,Cancer ,General Medicine ,medicine.disease ,Histone Deacetylase Inhibitors ,Clinical trial ,030104 developmental biology ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Pharmacodynamics ,Benzamides ,Cancer research ,Drug Evaluation ,Female ,Histone deacetylase ,business - Abstract
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.
- Published
- 2017