Histone deacetylases (HDACs) influence diverse cellular processes and may 
contribute to tumor development and progression by multiple mechanisms. Class I 
HDACs are often overexpressed in cancers contributing to a genome-wide 
epigenetic state permitting increased proliferation, and diminished apoptosis 
and cell differentiation. Class IIA and IIB isoenzymes may likewise contribute 
to tumorigenesis as components of specific intranuclear repressor complexes or 
regulators of posttranslational protein modifications. As HDAC inhibitors may 
counteract these tumorigenic effects several of these compounds are currently 
tested in clinical trials. HDAC inhibitors are also considered for urothelial 
carcinoma, where novel therapeutic drugs are urgently required. However, only 
modest antineoplastic activity has been observed with isoenzyme-unspecific 
pan-HDAC inhibitors. Therefore, inhibition of specific HDAC isoenzymes might be 
more efficacious and tumor-specific. Here, we systematically review knowledge on 
the expression, function and suitability as therapeutic targets of the 11 
classical HDACs in UC. Overall, the class I HDACs HDAC1 and HDAC2 are the most 
promising targets for antineoplastic treatment. In contrast, targeting HDAC8 and 
HDAC6 is likely to be of minor relevance in urothelial carcinoma. Class IIA 
HDACs like HDAC4 require further study, since their downregulation rather than 
upregulation could be involved in urothelial carcinoma pathogenesis.