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.
No comments:
Post a Comment