Epigenetic Therapy
A New Approach To Treat Cancer
Epigenetic mechanisms in normal cells:
Chromatin is made of repeating units of nucleosomes, which consist of 146 base pairs of DNA wrapped around an octamer of four core histone proteins (H3, H4, H2A and H2B).
Epigenetic mechanisms that modify chromatin structure can be divided into four main categories: DNA methylation, covalent histone modifications, non-covalent mechanisms such as incorporation of histone variants and nucleosome remodeling and non-coding RNAs including microRNAs (miRNAs).
These modifications work together to regulate the functioning of the genome by altering the local structural dynamics of chromatin, primarily regulating its accessibility and compactness. The interplay of these modifications creates an ‘epigenetic landscape’ that regulates the way the mammalian genome manifests itself in different cell types, developmental stages and disease states, including cancer. The distinct patterns of these modifications present in different cellular states serve as a guardian of cellular identity. Here, we will discuss the important aspects of the key epigenetic mechanisms present in normal cells.
Aberrant reprogramming of the epigenome in cancer:
The precise epigenomic landscape present in normal cells undergoes extensive distortion in cancer. These epimutations, along with widespread genetic alterations, play an important role in cancer initiation and progression. The cancer epigenome is characterized by global changes in DNA methylation and histone modification patterns as well as altered expression profiles of chromatin-modifying enzymes. These epigenetic changes result in global dysregulation of gene expression profiles leading to the development and progression of disease states. Epimutations can lead to silencing of tumor suppressor genes independently and also in conjunction with deleterious genetic mutations or deletions; thus, serving as the second hit required for cancer initiation according to the ‘two-hit’ model proposed by Alfred Knudso. In addition to inactivating tumor suppressors, epimutations can also promote tumorigenesis by activating oncogenes. The events that lead to initiation of these epigenetic abnormalities are still not fully understood. Nevertheless, since epigenetic alterations, like genetic mutations, are mitotically heritable, they are selected for in a rapidly growing cancer cell population and confer a growth advantage to tumor cells resulting in their uncontrolled growth.
The Essay on Whats The Difference Between A Cancer Cell And A Normal Cell
Cancer cells are abnormal cells and they have characteristics that can be associated with their ability to grow uncontrollably. Cancer cells are non-specialized, and divide uncontrollably. Cancer in situ is a tumor located in its place of origin. Malignant tumors establish new tumor distant from the primary tumors. Cancer cells characteristics distinguish them from normal cells. They have abnormal ...
Epigenetic therapy of cancer
The reversible nature of the profound epigenetic changes that occur in cancer has led to the possibility of ‘epigenetic therapy’ as a treatment option. The aim of epigenetic therapy is to reverse the causal epigenetic aberrations that occur in cancer, leading to the restoration of a ‘normal epigenome’. Many epigenetic drugs have been discovered in the recent past that can effectively reverse DNA methylation and histone modification aberrations that occur in cancer. DNA methylation inhibitors were among the first epigenetic drugs proposed for use as cancer therapeutics. The remarkable discovery that treatment with cytotoxic agents, 5-azacytidine (5-aza-CR) and 5-aza-2′-deoxycytidine (5-aza-CdR), lead to the inhibition of DNA methylation that induced gene expression and caused differentiationin cultured cells led to the realization of the potential use of these drugs in cancer therapy. These nucleoside analogs get incorporated into the DNA of rapidly growing tumor cells during replication and inhibit DNA methylation by trapping DNA methyltransferases onto the DNA, leading to their depletion inside the cell. This drug-induced reduction of DNA methylation causes growth inhibition in cancer cells by activating tumor suppressor genes aberrantly silenced in cancer.
The Term Paper on Cancer Is There An Effective Treatment
Introduction Purpose One of the many complications with cancer is that there are so many different types. Currently, there are 112 types of cancer, and there is an estimated 80 more types of cancer that are undiscovered. (United States Cancer Rates) That leads to as many different treatments as there are types of cancer. Figure 1, located after the Recommendations section, on page 8 displays the ...
5-Aza-CR (azacitidine) and 5-aza-CdR (decitabine) have now been FDA approved for use in the treatment of myelodysplastic syndromes and promising results have also emerged from the treatment of other hematological malignancies such as acute myeloid leukemia and chronic myeloid leukemia using these drugs. The possible clinical use of other improved DNA methylation inhibitors such as zebularine, which can be orally administered, is currently under investigation.Aberrant gene silencing in cancer is also associated with a concomitant loss of histone acetylation. Re-establishing normal histone acetylation patterns through treatment with HDAC inhibitors have been shown to have antitumorigenic effects including growth arrest, apoptosis and the induction of differentiation. Theseantiproliferative effects of HDAC inhibitors are mediated by their ability to reactivate silenced tumor suppressor genes. Suberoylanilide hydroxamic acid (SAHA), which is an HDAC inhibitor, has now been approved for use in clinic for treatment of T cell cutaneous lymphoma. Several other HDAC inhibitors such as depsipeptide and phenylbutyrate are currently under clinical trials.