Abstract
Epigenetics is essentially a phenotypical change in gene expression without any alteration of the DNA sequence; the emergence of epigenetics in cancer research and mainstream oncology is fueling new hope. However, it is not yet known whether this knowledge will translate to improved clinical management of ovarian cancer. In this malignancy, women are still undergoing chemotherapy similar to what was approved in 1978, which to this day represents one of the biggest breakthroughs for treating ovarian cancer. Although liquid tumors are benefiting from epigenetically related therapies, solid tumors like ovarian cancer are not (yet?). Herein, we will review the science of molecular epigenetics, especially DNA methylation, histone modifications and microRNA, but also include transcription factors since they, too, are important in ovarian cancer. Pre-clinical and clinical research on the role of epigenetic modifications is also summarized. Unfortunately, ovarian cancer remains an idiopathic disease, for the most part, and there are many areas of patient management, which could benefit from improved technology. This review will also highlight the evidence suggesting that epigenetics may have pre-clinical utility in pharmacology and clinical applications for prognosis and diagnosis. Finally, drugs currently in clinical trials (i.e., histone deacetylase inhibitors) are discussed along with the promise for epigenetics in the exploitation of chemoresistance. Whether epigenetics will ultimately be the answer to better management in ovarian cancer is currently unknown; but we hope so in the future.
Highlights
TO EPIGENETIC MODIFICATIONS genetic alterations, such as gene copy-number variations, contribute to the development of cancer, classical genetics alone does not account for all acquired characteristics of cancer cells
Epigenetic modifications among cancer cells result in aberrant gene expression via DNA methylation, histone modifications, and noncoding microRNAs and can include alterations among transcription factors [3], the latter is less often emphasized in epigenetics
This type of methylation is achieved by DNA methyltransferases (DNMTs), which are a family of enzymes that serve to transfer methyl groups onto DNA [5]
Summary
TO EPIGENETIC MODIFICATIONS genetic alterations, such as gene copy-number variations, contribute to the development of cancer, classical genetics alone does not account for all acquired characteristics of cancer cells. Epigenetic modifications among cancer cells result in aberrant gene expression via DNA methylation, histone modifications, and noncoding microRNAs (miRNAs) and can include alterations among transcription factors [3], the latter is less often emphasized in epigenetics. These modifications are associated with initiation and progression of ovarian cancers (Figure 1).
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