histone deacetylase inhibitors advancing therapeutic strategies in hematological and solid malignancies组蛋白脱乙酰酶抑制剂推进在血液和固体恶性肿瘤的治疗策略.pdfVIP

Pharmaceuticals 2010, 3, 2441-2469; doi:10.3390/ph3082441 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Histone Deacetylase Inhibitors: Advancing Therapeutic Strategies in Hematological and Solid Malignancies Leigh Ellis and Roberto Pili * Roswell Park Cancer Institute, Genitourinary Program, Grace Cancer Drug Center, Buffalo, NY 14263, USA; E-Mail: Leigh.Ellis@ (L.E.) * Author to whom correspondence should be addressed; E-Mail: Roberto.Pili@; Tel.: +1-716-845-3851; Fax: +1-716-845-4620. Received: 16 July 2010; in revised form: 30 July 2010 / Accepted: 2 August 2010 / Published: 4 August 2010 Abstract: Advancement in the understanding of cancer development in recent years has identified epigenetic abnormalities as a common factor in both tumorigenesis and refractory disease. One such event is the dysregulation of histone deacetylases (HDACs) in both hematological and solid tumors, and has consequently resulted in the development of HDAC inhibitors (HDACI) to overcome this. HDACI exhibit pleiotropic biological effects including inhibition of angiogenesis and the induction of autophagy and apoptosis. Although HDACI exhibit modest results as single agents in preclinical and clinical data, they often fall short, and therefore HDACI are most promising in combinational strategies with either standard treatments or with other experimental chemotherapies and targeted therapies. This review will discuss the induction of autophagy and apoptosis