Entinostat for treatment of solid tumors and hematologic malignancies

被引:100
作者
Knipstein, Jeffrey [1 ,2 ]
Gore, Lia [2 ,3 ]
机构
[1] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA
[2] Univ Colorado, Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO 80045 USA
[3] Univ Colorado, Early Phase Hematol Malignancies Program, Colorado Canc Ctr, Aurora, CO 80045 USA
关键词
entinostat; epigenetics; HDAC inhibitor; Phase I trial; Phase II trial; HISTONE-DEACETYLASE INHIBITOR; VIVO ANTITUMOR-ACTIVITY; PROSTATE-CANCER CELLS; INDUCE GROWTH ARREST; HDAC INHIBITORS; LUNG-CANCER; LEUKEMIA-CELLS; E-CADHERIN; PHASE-I; SELECTIVE INHIBITOR;
D O I
10.1517/13543784.2011.613822
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
:Introduction: 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. Areas covered: 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. Expert opinion: 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.
引用
收藏
页码:1455 / 1467
页数:13
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