Abstract
Epigenetic inactivation of tumour suppressor genes, in contrast to gene mutations,
can be modulated or reversed by small molecules. This has lead to several recent studies
of drugs targeting epigenetic mechanisms as novel cancer therapies. So far, epigenetic
therapies, including HDAC inhibitors and demethylating agents, show considerable activity
in haematological malignancies, but their value in the treatment of solid tumours
remains much more uncertain. This review will discuss some of the challenges that
are expected in the treatment of solid tumours with epigenetic therapies and discuss
approaches to overcome these obstacles. There is an increasing need for trials driven
by pharmacodynamic biomarkers for these agents, which are aimed at finding the optimum
biological dose rather than the maximal-tolerated dose, and also investigating their
use in combination with cytotoxics – for example as chemosensitisers. Such trials
already suggest that improved tumour delivery and specificity, with decreased normal
tissue toxicity, will be required to take full advantage of this class of agents in
solid tumours.
Keywords
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Article info
Publication history
Published online: February 12, 2009
Accepted:
January 6,
2009
Received:
October 13,
2008
Identification
Copyright
© 2009 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
