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báo cáo khoa học: "Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài:Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents | Tan et al. Journal of Hematology Oncology 2010 3 5 http www.jhoonline.Org content 3 1 5 JOURNAL OF HEMATOLOGY ONCOLOGY REVIEW Open Access Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents Jiahuai Tan1 Shundong Cang2 Yuehua Ma3 Richard L Petrillo1 Delong Liu3 Abstract Histone deacetylases HDACs can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors vorinostat has been approved by FDA for treating cutaneous T-cell lymphoma CTCL for patients with progressive persistent or recurrent disease on or following two systemic therapies. Other inhibitors for example FK228 PXD101 PCI-24781 ITF2357 MGCD0103 MS-275 valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents. Background Histones are among the most evolutionarily conserved proteins and the most abundant proteins bound to DNA in eukaryotic cells 1 . There are a total of five classes of them H1 H2A H2B H3 and H4 organized into two groups core histones H2A H2B H3 and H4 and linker histone H1 . Two each of the core histones form nucleosome particle by wrapping 147 base pairs of DNA. Histone H1 as a linker binds nucleosomes together and thus participates in a higher-order of histones as chromatin 2-4 . Chromatin undergoes modifications by changing its structure and chemical composition as cells .