Trapani Dario, Esposito Angela, Criscitiello Carmen, Mazzarella Luca, Locatelli Marzia, Minchella Ida, Minucci Saverio, Curigliano Giuseppe
a Division of Early Drug Development , European Institute of Oncology , Milan , Italy.
b Department of Oncology and Hematology , University of Milan , Milan , Italy.
Expert Opin Investig Drugs. 2017 Aug;26(8):965-971. doi: 10.1080/13543784.2017.1353077. Epub 2017 Jul 24.
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results. The emerging activity of entinostat in several clinical settings is evaluated by focusing on endocrine-resistant, HER2 positive and triple-negative breast cancer with promising activity in boosting the immune-system. Expert opinion: Entinostat, a synthetic benzamide derivative class I histone deacetylases (HDACs) inhibitor, inhibits cell proliferation and promotes apoptosis in breast cancer. Several results from clinical trials demonstrate that the addition of an epigenetic therapy to antiestrogen therapy may be an effective approach to targeting resistance pathways in breast cancer, particularly in hormone-positive disease. Agents such as entinostat may have a role in immunogenic modulation. Genetic and pharmacological inhibition studies identified HDAC as a key determinant in the reversal of carcinoma immune escape. This offers the rationale for combining HDAC inhibitors with immunotherapy, including therapeutic cancer vaccines.
乳腺癌占恶性肿瘤的29%。它是一种异质性疾病，涵盖一系列不同的分子亚型。表观遗传畸变可能通过DNA和组蛋白修饰影响基因表达，从而促进肿瘤进展和对抗肿瘤治疗产生耐药性。涵盖领域：本文探讨了恩替诺特在乳腺癌治疗中的潜在作用。讨论了评估恩替诺特的临床试验，重点介绍了临床前数据和早期临床研究结果。通过关注内分泌抵抗性、HER2阳性和三阴性乳腺癌，评估了恩替诺特在几种临床环境中的新出现的活性，其在增强免疫系统方面具有有前景的活性。专家观点：恩替诺特是一种合成苯甲酰胺衍生物I类组蛋白去乙酰化酶（HDACs）抑制剂，可抑制乳腺癌细胞增殖并促进其凋亡。多项临床试验结果表明，在抗雌激素治疗中添加表观遗传疗法可能是针对乳腺癌耐药途径的有效方法，尤其是在激素阳性疾病中。恩替诺特等药物可能在免疫原性调节中发挥作用。基因和药理学抑制研究确定HDAC是逆转癌症免疫逃逸的关键决定因素。这为将HDAC抑制剂与免疫疗法（包括治疗性癌症疫苗）联合使用提供了理论依据。
