About this Research Topic
Eukaryotic dynamic gene expression is based on gene-wide repression and its relief is a requirement for state or tissue developmental, cell differentiation, and disease processes. Nucleosomes are organized as a combination of DNA intertwined with nuclear proteins, called histones. Histone modulation is related to multiple post-translational modifications, including reversible acetylation of the amino-terminal group of lysines in these proteins; a balance between the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs, also known as lysine deacetylases or KDACs) tightly controls histone acetylation. HDACs play a critical role in transcription regulation by removing the acetyl groups of lysines on histone tails. Gene repression begins with the wrapping of DNA around histones in the nucleosome, and it is relieved by unwrapping of the DNA through chromatin-remodeling complexes. Thus, acetylation and deacetylation are presently considered important epigenetic mechanisms in regulation of gene expression and the remodeling of chromatin.
Similarly, the importance of chromatin-remodeling complexes is widespread, with many complexes serving specific functional roles. Recent genome-wide sequencing studies have unmasked a major, previously unexpected, contribution of chromatin regulatory factors to human diseases, including cancer. Given that histone modification modulates chromatin structure and gene expression, it is not surprising that abnormal alterations in histone acetylation are associated with cancer development. Hence, the use of epigenetic therapies in the treatment of solid tumors is also emerging as a viable therapeutic route. Previous research studies demonstrate that epigenetic abnormalities are closely associated with carcinogenesis, providing the use of epigenetic-based therapies such as HDAC inhibitors (HDACis). A number of compounds that inhibit HDAC activity have now been developed and characterized and seem to cause the arrest of cell growth, differentiation and/or apoptosis, impacting on tumor growth in in vitro and in vivo experiments. For the above presented reasons, studies involving therapies using HDACs are important to better our understanding of the relationship between cancer and these enzymes, in a way that could open the possibility of the development of therapeutic treatments regarding epigenetic mechanisms.
Topics of interest for this Research Topic include, but are not limited to:
• Design and synthesis of novel HDACi involved with functional anticancer therapy.
• Epigenetic targeting via HDACi in tumor cells.
• Clinical studies and their significance using HDACi in cancer treatment.
• Assessment of HDACi related to immune response and immunotherapy in cancer.
• Targeting HDACs with design and activity of new HDACi as an anticancer strategy.
• Synergism therapy with HDACi for improved cancer treatment.
• Structural requirements of HDACi to improve activity and selectivity against cancer.
• Synergism effect of HDACi, combination with chemotherapy or heavy ion radiotherapy for cancer treatment.
• Enzyme-instructed self-assembly of HDACi with enhanced selectivity and anticancer efficiency.
• Understand HDACi and cancer cell signaling (cytoskeleton organizing, apoptosis, autophagy and other signals) and to find targets for cancer therapy.
• Influence of HDACi in cancer stem cells, cancer invasion/metastasis and viral infection-based cancer cells.
Keywords: Drugs, HPV, Cancer, Cellular, Molecular, Biology
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