Abstract |
The protein methyltransferases (PMT) constitute a large and important class of enzymes that catalyze site-specific methylation of lysine or arginine residues on histones and other proteins. Site-specific histone methylation is a critical component of chromatin regulation of gene transcription-a pathway that is often genetically altered in human cancers. Oncogenic alterations (e.g., mutations, chromosomal translocations, and others) of PMTs, or of associated proteins, have been found to confer unique dependencies of cancer cells on the activity of specific PMTs. Examples of potent, selective small-molecule inhibitors of specific PMTs are reviewed that have been shown to kill cancers cells bearing such oncogenic alterations, while having minimal effect on proliferation of nonaltered cells. Selective inhibitors of the PMTs, DOT1L and EZH2, have entered phase I clinical studies and additional examples of selective PMT inhibitors are likely to enter the clinic soon. The current state of efforts toward clinical testing of selective PMT inhibitors as personalized cancer therapeutics is reviewed here.
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Authors | Robert A Copeland |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 19
Issue 23
Pg. 6344-50
(Dec 01 2013)
ISSN: 1557-3265 [Electronic] United States |
PMID | 23958745
(Publication Type: Journal Article, Review)
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Copyright | ©2013 AACR. |
Chemical References |
- Antineoplastic Agents
- Protein Methyltransferases
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Catalytic Domain
- Clinical Trials as Topic
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Molecular Targeted Therapy
- Mutation
- Neoplasms
(drug therapy, enzymology, genetics)
- Protein Methyltransferases
(antagonists & inhibitors, chemistry, physiology)
- Protein Processing, Post-Translational
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