Drug Development Unit, Division of Clinical Sciences, The Institute of Cancer Research/The Royal Marsden, Downs Road, Sutton, Surrey, SM2 5PT, UK.
Expert Opin Investig Drugs. 2011 Dec;20(12):1723-32. doi: 10.1517/13543784.2011.629604. Epub 2011 Nov 3.
Histone deacetylase (HDAC) inhibitors have recently emerged as a novel and active class of anticancer agents. Belinostat is one member of the class that has been tested as a single agent and in combination with other chemotherapies and biological agents in the treatment of solid tumors and lymphoma.
A literature search of pre-clinical and clinical studies of belinostat was performed. The data from these studies were analysed to summarise the progress of belinostat from Phase I to a current pivotal trial in peripheral T-cell lymphoma. The parallel development of appropriate biomarker analysis is also discussed.
Belinostat has demonstrated significant clinical activity in T-cell lymphomas. Although its activity as a single agent in solid tumors has been less compelling, the emerging results from combination trials are promising. However, the basis for the activity of belinostat, like that of other HDAC inhibitors, remains to be truly defined and the identification of predictive and prognostic biomarkers of activity should be established to further progress the development of this compound.
组蛋白去乙酰化酶(HDAC)抑制剂最近成为一种新型的、活跃的抗癌药物。贝林司他是该类药物中的一种,已作为单一药物以及与其他化疗药物和生物制剂联合用于治疗实体瘤和淋巴瘤进行了试验。
对贝林司他的临床前和临床研究进行了文献检索。对这些研究的数据进行了分析,以总结贝林司他从 I 期到目前外周 T 细胞淋巴瘤关键试验的进展。还讨论了相关生物标志物分析的平行发展。
贝林司他在 T 细胞淋巴瘤中显示出显著的临床活性。尽管其作为单一药物在实体瘤中的活性不那么引人注目,但联合试验的新结果令人鼓舞。然而,像其他 HDAC 抑制剂一样,贝林司他的作用基础仍有待真正确定,应确定预测和预后活性的生物标志物,以进一步推进该化合物的开发。