期刊
CANCER LETTERS
卷 280, 期 2, 页码 192-200出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.03.013
关键词
Histone deacetylase inhibitors; Epigenetic therapy; Hematological malignancies; Solid tumors; Surrogate markers; Cancer
类别
Histone deacetylase inhibitors (HDACIs) constitute a novel class of targeted drugs that alter the acetylation status of histones and other important cellular proteins. These agents modulate chromatin structure leading to transcriptional changes, induce pleiotropic effects on functional pathways and activate cell death signaling in cancer cells. Anti-neoplastic activity in vitro was shown in several experimental models of cancer, but the exact mechanism of cytotoxicity and responses are not clearly understood. Phase I/II clinical trials of various HDACIs as single agents conducted to date have shown substantial activity in cutaneous T cell lymphoma (CTCL), preliminary activity in Hodgkin's disease and modest activity in myeloid neoplasms. Responses have been rare in solid tumors. Several agents are being tested in combination therapy clinical trials, either as chemosensitizers for cytotoxic chemotherapy or radiation therapy, or in association with DNA methylation inhibitors based on in vitro synergy. In this review, we focus on recent basic and clinical data that highlight the anti-neoplastic role of HDACIs. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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