In vitro basis for treatment with hypomethylating agents and histone deacetylase inhibitors: can epigenetic changes be used to monitor treatment?

Steven D. Gore

doi:10.1016/S0145-2126(09)70226-7

In vitro basis for treatment with hypomethylating agents and histone deacetylase inhibitors: can epigenetic changes be used to monitor treatment?

Steven D. Gore

Research output: Contribution to journal › Article › peer-review

Abstract

Hematopoietic disorders such as myelodysplastic syndromes (MDS) show a high frequency of methylation of tumor suppressor genes. DNA methyltransferase (DNMT) inhibitors such as azacitidine and decitabine are used to target DNA methylation in MDS patients. Combining these drugs with histone deacetylase (HDAC) inhibitors in vitro resulted in synergistic tumor suppressor gene re-expression. Several phase I trials have examined methylation, gene expression and DNA damage as markers of clinical response to DNMT and HDAC inhibitors, with conflicting results. Trials are ongoing to investigate early methylation changes and DNA damage markers to understand the mechanisms of these drugs and as potential predictors of clinical response.

Original language	English (US)
Pages (from-to)	S2-S6
Journal	Leukemia Research
Volume	33
Issue number	SUPPL. 2
DOIs	https://doi.org/10.1016/S0145-2126(09)70226-7
State	Published - Dec 2009
Externally published	Yes

Keywords

Azacitidine
Cancer epigenetics
DNA methyltransferase inhibitors
Histone deacetylase inhibitors
Myelodysplastic syndromes treatment
Predictors of response

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1016/S0145-2126(09)70226-7

Cite this

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title = "In vitro basis for treatment with hypomethylating agents and histone deacetylase inhibitors: can epigenetic changes be used to monitor treatment?",

abstract = "Hematopoietic disorders such as myelodysplastic syndromes (MDS) show a high frequency of methylation of tumor suppressor genes. DNA methyltransferase (DNMT) inhibitors such as azacitidine and decitabine are used to target DNA methylation in MDS patients. Combining these drugs with histone deacetylase (HDAC) inhibitors in vitro resulted in synergistic tumor suppressor gene re-expression. Several phase I trials have examined methylation, gene expression and DNA damage as markers of clinical response to DNMT and HDAC inhibitors, with conflicting results. Trials are ongoing to investigate early methylation changes and DNA damage markers to understand the mechanisms of these drugs and as potential predictors of clinical response.",

keywords = "Azacitidine, Cancer epigenetics, DNA methyltransferase inhibitors, Histone deacetylase inhibitors, Myelodysplastic syndromes treatment, Predictors of response",

author = "Gore, {Steven D.}",

note = "Funding Information: The author received editorial support from Excerpta Medica in the preparation of this manuscript, funded by Celgene Corporation. The author is fully responsible for content and editorial decisions for this manuscript. ",

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doi = "10.1016/S0145-2126(09)70226-7",

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T1 - In vitro basis for treatment with hypomethylating agents and histone deacetylase inhibitors

T2 - can epigenetic changes be used to monitor treatment?

AU - Gore, Steven D.

N1 - Funding Information: The author received editorial support from Excerpta Medica in the preparation of this manuscript, funded by Celgene Corporation. The author is fully responsible for content and editorial decisions for this manuscript.

PY - 2009/12

Y1 - 2009/12

N2 - Hematopoietic disorders such as myelodysplastic syndromes (MDS) show a high frequency of methylation of tumor suppressor genes. DNA methyltransferase (DNMT) inhibitors such as azacitidine and decitabine are used to target DNA methylation in MDS patients. Combining these drugs with histone deacetylase (HDAC) inhibitors in vitro resulted in synergistic tumor suppressor gene re-expression. Several phase I trials have examined methylation, gene expression and DNA damage as markers of clinical response to DNMT and HDAC inhibitors, with conflicting results. Trials are ongoing to investigate early methylation changes and DNA damage markers to understand the mechanisms of these drugs and as potential predictors of clinical response.

AB - Hematopoietic disorders such as myelodysplastic syndromes (MDS) show a high frequency of methylation of tumor suppressor genes. DNA methyltransferase (DNMT) inhibitors such as azacitidine and decitabine are used to target DNA methylation in MDS patients. Combining these drugs with histone deacetylase (HDAC) inhibitors in vitro resulted in synergistic tumor suppressor gene re-expression. Several phase I trials have examined methylation, gene expression and DNA damage as markers of clinical response to DNMT and HDAC inhibitors, with conflicting results. Trials are ongoing to investigate early methylation changes and DNA damage markers to understand the mechanisms of these drugs and as potential predictors of clinical response.

KW - Azacitidine

KW - Cancer epigenetics

KW - DNA methyltransferase inhibitors

KW - Histone deacetylase inhibitors

KW - Myelodysplastic syndromes treatment

KW - Predictors of response

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In vitro basis for treatment with hypomethylating agents and histone deacetylase inhibitors: can epigenetic changes be used to monitor treatment?

Abstract

Keywords

ASJC Scopus subject areas

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