Novel Indications of Epigenetic Therapy in Ovarian Cancer

Abstract

Early diagnosis and intervention are some of the longstanding challenges associated with ovarian cancer, which is the leading cause of gynecologic cancer mortality. While the majority of patients who present with advanced stage disease at time of diagnosis will initially respond to traditional combination platinum and taxane-based chemotherapy in conjunction with cytoreductive surgery, approximately 70% will ultimately recur due to chemoresistance within the first two years. Intratumor heterogeneity is proposed to be a leading factor in the development of chemoresistance and resultant poorer outcomes for those with recurrent or advanced stage disease. Both inherent and acquired mechanisms of chemoresistance are postulated to be a result of alterations in gene expression, also known as epigenetic modifications. Therefore, epigenetic therapy is a pivotal avenue which allows for reversal of chemoresistance in cancer through the targeting of aberrant mutations. In this chapter, we discuss how these epigenetic modifications prove to be promising targets in cancer therapy leading to heightened drug sensitivity and improved patient survival outcomes.

Influence of Aberrant Epigenetic Changes and the Tumor Microenvironment in Ovarian Cancer Metastasis

“…Ovarian cancer develops key genetic mutations that allow cells to grow uncontrollably, invade into nearby tissues, and to evade immune system defenses (6). However, recent discoveries show that epigenetic modifications are also important for ovarian cancer cell to propagate and metastasize.…”

“…The current standard treatment for ovarian cancer is cytoreductive surgery, a heroic attempt at complete removal of the disease, followed by chemotherapy (6). Surgery alone is often not curative due to the persistence of microscopic, metastatic, residual disease (6).…”

“…The current standard treatment for ovarian cancer is cytoreductive surgery, a heroic attempt at complete removal of the disease, followed by chemotherapy (6). Surgery alone is often not curative due to the persistence of microscopic, metastatic, residual disease (6). With the addition of chemotherapy, the potential for a cure is increased through the attempted eradication of residual microscopic disease that cannot be seen during surgery (7).…”

“…As new modern therapies are developed, epigenetic therapies are promising in the treatment of tumor metastasis. Epigenetic therapy can directly target cells with aberrant epigenetic modifications; so, cancer cells and its associated tumor microenvironment can be specifically targeted while sparing healthy tissue from toxic side effects (6). Epigenetics, the study of the alteration of gene expression without associated changes to the DNA sequence, involves methylation or acetylation of DNA by specific enzymes that alter gene transcription (6).…”

“…Epigenetic therapy can directly target cells with aberrant epigenetic modifications; so, cancer cells and its associated tumor microenvironment can be specifically targeted while sparing healthy tissue from toxic side effects (6). Epigenetics, the study of the alteration of gene expression without associated changes to the DNA sequence, involves methylation or acetylation of DNA by specific enzymes that alter gene transcription (6). Ovarian cancer cells develop these aberrant epigenetic modifications that are preserved during cell division and help these cells to gain invasive, chemoresistant, and metastatic properties.…”