To create better effects in cancer
treatment, various therapies such as chemotherapy, biologic therapy, or
radiation therapy are employed either in either a separate or combined way.
Recently, researchers have started to reconsider the scene from a different
perspective and they found the epigenetic control of gene expression played an
important role in cancer progression and resistance. Therefore, agents that
modify the epigenetic environment of tumor might be an innovative solution for
this problem. As shown by preclinical data, HDAC inhibitors are very effective anticancer
agents either as monotherapies or in conjunction with other treatments. Since
then, many HDAC inhibitors are actively studied and two of their
representatives - vorinostat and depsipeptide – has recently gained FDA
approval for treating T-cell lymphoma.
What
are HDAC inhibitors?
HDAC (histone deacetylase) inhibitors are a
family of eleven zinc-dependent enzymes that have gained major interest as
therapeutic targets, mainly in cancer research. HDAC inhibitors have a long
history of use in a wide range of diseases, including neurological diseases, immune
disorders, cancers, parasitic and inflammatory diseases. In this article, we
are going to focus on two main diseases.
HDAC
inhibitors to treat breast cancer
As the most frequently diagnosed cancer,
breast cancer has inflicted unspeakable pain to women worldwide. Based on
statistics from the American Cancer Society, nearly one in eight women in
industrialized countries will develop breast cancer during their lifetime. It
also shows that more people are dying from this disease recently. Considering that
HDACs play an impactful role on chromatin remodeling and epigenetics, their
inhibitors have become very promising anticancer treatment candidates for breast
cancer, either as single agents or in combination therapy. Molecules having
been actively researched include: trichostatin A, panobinostat, valproic acid,
sodium butyrate, FTY720, YCW1, etc. All are showing positive preclinical
effects.
Overall, HDAC inhibitors presents an
attractive field for targeted therapy against breast cancer. To target multiple
oncogenic signaling pathways, future therapies will focus more on combining
HDAC inhibitors with other already well-established strategies like
chemotherapy.
HDAC
inhibitors to treat Alzheimer’s disease
Despite the fact that HDAC inhibitors were initially
applied to the cancer therapy, another group of scientists found in 2008 that HDAC
inhibitors might also be an effective strategy for treating neurodegenerative
disorders. Alzheimer’s disease (AD) is one of them with symptoms like learning
and memory impairment in the elderly. Recent studies have found that HDACs
inhibitors are novel promising therapeutic agents for treating AD as well as other
neurodegenerative diseases. The future is bright while key issues still exist
and need to be addressed in terms of the enhancement of specificity, efficacy
and avoiding side effects.
