Current limitations and future opportunities for epigenetic therapies

被引：0

作者：

Cherblanc, F. ^{[2
]}

Chapman-Rothe, N. ^{[1
]}

Brown, R. ^{[1
]}

Fuchter, M. J. ^{[2
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Ovarian Canc Act Ctr, Epigenet Unit, Dept Surg & Canc, London W12 ONN, England

[2] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AZ, England

来源：

FUTURE MEDICINAL CHEMISTRY | 2012年 / 4卷 / 04期

关键词：

HISTONE DEACETYLASE INHIBITORS; PROTEIN LYSINE METHYLTRANSFERASES; PHASE-II TRIAL; S-ADENOSYLHOMOCYSTEINE HYDROLASE; SUBEROYLANILIDE HYDROXAMIC ACID; CPG ISLAND HYPERMETHYLATION; MESSENGER-RNA EXPRESSION; TUMOR-SUPPRESSOR GENES; ACUTE-LEUKEMIA CELLS; DNA METHYLATION;

D O I：

10.4155/FMC.12.7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This article reviews progress in epigenetic therapies that hope to improve the treatment of cancer. Tumors show widespread, aberrant epigenetic changes, leading to changes in the expression of genes involved in all the hallmarks of cancer. These epigenetic changes can potentially be reversed using small-molecule inhibitors of enzymes involved in maintenance of the epigenetic state. DNA-demethylating agents and histone deacetylase inhibitors have shown anti-tumor activity against certain hematological malignancies; however, their activity in solid tumors remains more uncertain. Major challenges remain in delivery of epigenetic therapy, maintenance of a pharmacodynamic response and achievement of a therapeutic index. We believe histone lysine methyl transferases are a highly promising epigenetic target, which has yet to be clinically exploited. Crystallographic studies on histone lysine methyl transferases provide insights into their mechanism and specificity crucial for the design and development of small-molecule inhibitors.

引用

页码：425 / 446

页数：22

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