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Monday 2 April 2018

Mutational and Epimutational Analysis of Cell Death- Resistant Tumor Cells: Clues to Molecular Carcinogenesis and Cancer Therapy

                                  http://austinpublishinggroup.com/mutagenesis/online-first.php


Canceris a versatile complex disease and the development of a wide arsenal of treatment options is based upon piles of accumulated basic molecular research. This basis increasingly enhanced our knowledge of fundamental mechanisms underlying tumorigenesis. Besides studies involving in-vivo studies using patient´s material and xenografted mice, the performance of in-vitro experiments using tumor cells has led to the accumulation of a huge amount of data and significant progress. Among these insights was the revelation of the development of oncogenic transformation at several cellular levels due to silenced tumor suppressor genes, gain-of-function of oncogenes, loss-of cell death resistance, dysregulated intracellular signaling pathways, epithelial to mesenchymal transitions and dysregulated metabolism.

Genetic irregularities have been considered as distinctive features of a tumor cell since a long time. Analysis of tumor-specific mutations in human genomic DNA was initially demonstrated by sequencing the Kras gene. For the generation of in-vitro insights obtained of tumor biology and genetics since then, tumor-derived cell lines have taken over an important role. Across a wide array of studies, they have been tools of choice for gene and cellular pathway analysis that are impaired by diverse oncogenic events. They are also exceptionally indispensable for the screening of novel anticancer drugs.


In recent times, furthermore, epigenetic studies gained increasing significance in reports investigating the development of cancer. For this purpose, deviant epigenome including the misguided expression of HDACs activity has been defined to some extent in diverse tumor entities. As a result, it was concluded that aberrant epigenetic patterns such as DNA methylation and histone modifications are very common in tumor cells. Histone modifications, predominantly acetylation or deacetylation, are executed by different enzyme classes of histone acetyltransferases (HAT) and histone de-acetylases (HDAC), respectively. Nevertheless, HDAC not only catalyze the removal of the acetyl groups from histones, but also from non-histone proteins and enable pharmacological interference by different kind of inhibitors. The physiological functions of HDAC are still not fully elucidated but involve key cellular processes such as transcriptional regulation, apoptosis, cell cycle control, and autophagy that are involved in tumorigenesis. Conclusively, cancer is furthermore not only regarded as a pathologic condition of altered genetic, but also of epigenetic, deregulation.







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