Discovery and development of SAHA as an anticancer agent Journal Article


Author: Marks, P. A.
Article Title: Discovery and development of SAHA as an anticancer agent
Abstract: The path to the discovery of suberoylanilide hydroxamic acid (SAHA, vorinostat) began over three decades ago with our studies designed to understand why dimethylsulfoxide causes terminal differentiation of the virus-transformed cells, murine erythroleukemia cells. SAHA can cause growth arrest and death of a broad variety of transformed cells both in vitro and in vivo at concentrations that have little or no toxic effects on normal cells. It was discovered that SAHA inhibits the activity of histone deacetylases (HDACs), including all 11 known human class I and class II HDACs. HDACs have many protein targets whose structure and function are altered by acetylation including histones and non-histone proteins component of transcription factors controlling gene expression and proteins that regulate cell proliferation, migration and death. SAHA is in clinical trials and has significant anticancer activity against both hematologic and solid tumors at doses well tolerated by patients. A new drug application has been approved for SAHA (vorinostat) treatment of cutaneous T-cell lymphoma. © 2007 Nature Publishing Group All rights reserved.
Keywords: protein expression; fludarabine; clinical trial; drug tolerability; fatigue; review; fluorouracil; diarrhea; drug efficacy; drug potentiation; drug withdrawal; monotherapy; nonhuman; solid tumor; antineoplastic agents; capecitabine; antineoplastic agent; protein function; anorexia; cell proliferation; animals; cell death; imatinib; metastasis; apoptosis; bortezomib; enzyme inhibition; multiple myeloma; breast cancer; gene expression; gene expression profiling; dehydration; cell differentiation; antineoplastic activity; cytotoxicity; drug effect; enzyme activity; cell line, tumor; drug design; kidney carcinoma; hodgkin disease; prostate cancer; cutaneous t cell lymphoma; hematologic malignancy; drug mechanism; neuroblastoma; enzyme inhibitors; cell transformation; colon cancer; tumor necrosis factor related apoptosis inducing ligand; promyelocytic leukemia; murinae; mesothelioma; vorinostat; histone deacetylase inhibitors; cell migration; cell cycle arrest; urogenital tract tumor; thyroid cancer; flavopiridol; isotretinoin; protein structure; trastuzumab; larynx cancer; histones; histone deacetylases; retinoic acid; drug binding; clinical trials; myeloma; histone deacetylase 1; histone deacetylase 2; erythroleukemia; deacetylases
Journal Title: Oncogene
Volume: 26
Issue: 9
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 2007-02-26
Start Page: 1351
End Page: 1356
Language: English
DOI: 10.1038/sj.onc.1210204
PUBMED: 17322921
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 167" - "Export Date: 17 November 2011" - "CODEN: ONCNE" - "Source: Scopus"
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  1. Paul Marks
    147 Marks