Abstract
Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.
Highlights
Cancer chemotherapy has been one of the major medical advances in the last few decades
histone deacetylases (HDAC) are involved in different cellular pathways and functions; further studies are necessary to disclose all their functions and cellular interactions, which might result in development of more efficient therapy with HDAC inhibitors
HDAC inhibitors seem to be a promising group of anti-cancer drugs, in combination with other anti-cancer drugs and/or radiotherapy
Summary
Cancer chemotherapy has been one of the major medical advances in the last few decades. The drugs used for this therapy have a narrow therapeutic index, and the produced responses are often only palliative as well as unpredictable Such approaches, directed toward certain biomacromolecules, do not discriminate between rapidly dividing non-malignant and cancer cells. HDAC1 is highly expressed in prostate, gastric, lung, esophageal, colon and breast cancers [6,7,8]. We describe different classes of HDAC inhibitors and mechanisms of their actions, and discuss novel data found in several preclinical experiments and clinical studies. We discuss their combination with other therapeutic modalities, with DNA-damaging compounds
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