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.

Histone methylation is important in the regulation of genes expression, and thus its dysregulation has been observed in various cancers. KDM5 enzymes are capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4) which makes them potential players in the downregulation of tumor suppressors, but could also suggest that their activity repress oncogenes. Depending on the methylation site, their effect on transcription can be either activating or repressing. There is emerging evidence for deregulation of KDM5A/B/C/D and important phenotypic consequences in various types of cancer. It has been suggested that the KDM5 family of demethylases plays a role in the appearance of drug tolerance. Drug resistance remains a challenge to successful cancer treatment. This review summarizes recent advances in understanding the functions of KDM5 histone demethylases in cancer chemoresistance and potential therapeutic targeting of these enzymes, which seems to prevent the emergence of a drug‐resistant population.

Cancer despite the introduction of new targeted therapy remains for many patients a fatal disease. Nanotechnology in cancer medicine has emerged as a promising approach to defeat cancer. Targeted delivery of anti-cancer drugs by different nanosystems promises enhanced drug efficacy, selectivity, better safety profile and reduced systemic toxicity. The article presents an overview of recent developments in cancer nanomedicine. We focus on approved anti-cancer medical products and on the results of clinical studies, highlighting that liposomal and micellar cytostatics or albuminbased nanoparticles have less side effects and are more efficient than "free" drugs. In addition, we discuss results of in vitro and in vivo preclinical studies with lipid, inorganic and polymer nanosystems loaded by anticancer drugs which according to our meaning are important for development of new nanodrugs. Pharmacokinetic characteristics of nanodrugs are discussed and characterization of major nanotechnology systems used for cancer nanomedicine is presented.

Local application of anticancer agents prolongs the presence time and increases the concentration of drug in the target place and therefore may reduce serious side effects compared to drug systemic administration. The preparation of fibrous materials of polylactide (PLA) and polyethylene glycol (PEG) loaded with paclitaxel (PTX, 1 or 10 wt%) is presented. Scanning electron microscopy proves that PTX is homogeneously incorporated into the fibers. The addition of PEG of various molecular weights (6, 20, or 35 kDa) ensures the release of significantly higher amounts of hydrophobic PTX in a prolonged release time compared to the fibers containing PTX only. Present PLA-PEG fibrous carriers can serve as a drug depot for PTX since they exhibit significant toxicity for cancer cell lines in several-day experiment. They are promising for local recurrence therapy, where the initial release is efficient to kill tumor cells and continued release can prevent their subsequent proliferation.