The emerging role of histone deacetylase (HDAC) inhibitors in urological cancers

What's known on the subject? and What does the study add? A growing body of evidence supports the anti‐cancer effect of histone deacetylase inhibitors (HDACi) in vitro, via multiple pathways, and many Phase I clinical trials have shown them to be well‐tolerated in a range of malignancies. Combi...

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Bibliographic Details
Published in:BJU international Vol. 111; no. 4; pp. 537 - 542
Main Authors: Sharma, Naomi L., Groselj, Blaz, Hamdy, Freddie C., Kiltie, Anne E.
Format: Journal Article
Language:English
Published: Oxford Wiley-Blackwell 01.04.2013
Subjects:
Animals
Antineoplastic Agents - therapeutic use
Biological and medical sciences
cancer
Clinical Trials as Topic
Combined Modality Therapy
combined therapy
Disease Models, Animal
HDAC inhibitor
Histone Deacetylase Inhibitors - therapeutic use
Histone Deacetylases - drug effects
Histone Deacetylases - genetics
Humans
In Vitro Techniques
Male
Medical sciences
Molecular Targeted Therapy - methods
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Nephrology. Urinary tract diseases
Prognosis
Prospective Studies
Radiotherapy, Adjuvant
Risk Assessment
Survival Rate
Treatment Outcome
Tumors
Urologic Neoplasms - drug therapy
Urologic Neoplasms - genetics
Urologic Neoplasms - mortality
Urologic Neoplasms - pathology
urology
combined therapy
Histone deacetylase
Histone deacetylase inhibitor
Nephrology
Urinary system
HDAC inhibitor
Combined treatment
Malignant tumor
Urinary tract
Urology
Cancer
ISSN:1464-4096, 1464-410X, 1464-410X
Online Access:Get full text
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Summary:What's known on the subject? and What does the study add? A growing body of evidence supports the anti‐cancer effect of histone deacetylase inhibitors (HDACi) in vitro, via multiple pathways, and many Phase I clinical trials have shown them to be well‐tolerated in a range of malignancies. Combined therapies, including with radiation, present an exciting area of current and planned study. This review summarises the evidence to date, including pre‐clinical data and clinical trials, of the anti‐cancer effect of HDACi in urological cancers. It provides an overview of epigenetics and the mechanisms of action of HDACi. It suggests areas of future development, including the current challenges for the successful introduction of HDACi into clinical therapy. Epigenetic modifications are known to play a critical role in the development and progression of many cancers. The opposing actions of histone deacetylases (HDACs) and histone acetyltransferases (HATs) modify chromatin and lead to epigenetic gene regulation, in addition to wider effects on non‐histone proteins. There is growing interest in the clinical application of HDAC inhibitors (HDACi) in cancer. HDACi have been shown to inhibit cancer cell growth both in vitro and in vivo and recent clinical trials have shown encouraging results in various urological cancers. In this review, we discuss the existing evidence and potential role for HDACi in urological malignancies, including in combined therapies.
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ISSN:1464-4096
1464-410X
1464-410X
DOI:10.1111/j.1464-410X.2012.11647.x