TY - JOUR
T1 - Histone deacetylase inhibitors
T2 - A review of their clinical status as antineoplastic agents
AU - Garcia-Manero, Guillermo
AU - Issa, Jean Pierre
N1 - Funding Information:
G. G.-M. is the recipient of a Career Development Award from the American Society of Clinical Oncology and a Physician-Scientist Award from the University of Texas M.D. Anderson Cancer Center funded by the Commonwealth Cancer Foundation for Research.
PY - 2005
Y1 - 2005
N2 - The histone code refers to specific modifications in the biochemical composition of nucleosome-associated histone proteins involved in the regulation of gene transcription. These modifications include, among several, acetylation, methylation, and phosphorylation of several histone amino acid residues and are associated with different states of chromatin configuration and gene expression. In particular, acetylation of specific residues in histories H3 and H4 has been associated with an open chromatin configuration and a permissive gene transcription state. This particular modification is regulated by several enzymatic activities with the capacity to either transfer acetyl groups or to induce histone deacetylation. This last activity is associated with gene silencing. Several agents have been shown to have histone deacetylase inhibitory activity (HDACI). In vitro, experiments in multiple neoplastic cancer cell lines have demonstrated that treatment with HDACIs results in increased global and gene specific histone acetylation, and reactivation of aberrantly silenced genes. This phenomenon has been associated with cell differentiation and induction of apoptosis. Based on these observations, several of these agents are now in clinical development both for solid tumor and hematological malignancies. In this article, we provide a brief introduction to the field of histone deacetylation inhibition in cancer and review the most relevant clinical data so far published.
AB - The histone code refers to specific modifications in the biochemical composition of nucleosome-associated histone proteins involved in the regulation of gene transcription. These modifications include, among several, acetylation, methylation, and phosphorylation of several histone amino acid residues and are associated with different states of chromatin configuration and gene expression. In particular, acetylation of specific residues in histories H3 and H4 has been associated with an open chromatin configuration and a permissive gene transcription state. This particular modification is regulated by several enzymatic activities with the capacity to either transfer acetyl groups or to induce histone deacetylation. This last activity is associated with gene silencing. Several agents have been shown to have histone deacetylase inhibitory activity (HDACI). In vitro, experiments in multiple neoplastic cancer cell lines have demonstrated that treatment with HDACIs results in increased global and gene specific histone acetylation, and reactivation of aberrantly silenced genes. This phenomenon has been associated with cell differentiation and induction of apoptosis. Based on these observations, several of these agents are now in clinical development both for solid tumor and hematological malignancies. In this article, we provide a brief introduction to the field of histone deacetylation inhibition in cancer and review the most relevant clinical data so far published.
KW - Acetylation
KW - Histone
KW - Histone deacetylase inhibitors
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U2 - 10.1080/07357900500283119
DO - 10.1080/07357900500283119
M3 - Review article
C2 - 16305991
AN - SCOPUS:33344456652
SN - 0735-7907
VL - 23
SP - 635
EP - 642
JO - Cancer Investigation
JF - Cancer Investigation
IS - 7
ER -