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Researchers Identify Enzymes Associated With Chemoresistance in Ovarian Cancer

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Key Points

  • Two epigenetic regulators, HDAC1 and DNMT1, were found to be highly associated with the silencing of RGS10 expression in chemoresistant ovarian cancer cells.
  • Decreasing the expression of HDAC1 and DNMT1 and blocking their activity significantly increased RGS10 expression and cell death and also decreased the binding of HDAC1 to RGS10 in chemoresistant cells.
  • The research supports inhibition of HDAC1 and DNMT1 as an adjuvant therapeutic approach to overcoming chemoresistance in ovarian cancer.

Inhibiting enzymes that cause changes in gene expression could decrease chemotherapy resistance in patients with ovarian cancer, according to research by Cacan et al. The study investigated the silencing of RGS10 expression in ovarian cells by epigenetics and identified two epigenetic regulators, HDAC1, a histone deacetylase, and DNMT1, a DNA methyl transferase. The researchers found that decreasing the expression of HDAC1 and DNMT1 and blocking their activity significantly increased RGS10 expression and cell death and also decreased the binding of HDAC1 to RGS10 in chemoresistant cells. The study is published in PLOS ONE.

Potential New Therapeutic Approach

In a previous study, the researchers found the expression of the protein RGS10, which regulates ovarian cancer cell growth and survival, is suppressed in ovarian cancer cells that are chemoresistant. They also found that the suppression was caused by DNA methylation and histone deacetylation.

The researchers’ new findings suggest that HDAC1 and DNMT1 contribute to the suppression of RGS10 during acquired chemoresistance and support inhibition of HDAC1 and DNMT1 as an adjuvant therapeutic approach to overcoming chemoresistance in ovarian cancer.

“Ovarian cancer is usually treated by surgery followed by chemotherapy, but because it’s typically found fairly late, ovarian cancer is often refractory to chemotherapy,” Susanna Greer, PhD, coauthor of the study and Associate Professor in the Department of Biology at Georgia State University, said in a statement. “You have tumors that initially respond to chemotherapy and then don’t. Ovarian cancer is the eighth most commonly diagnosed cancer in U.S. women, but due to its late diagnosis, causes more deaths than any other cancer of the female reproductive system.”

Ovarian Cancer Incidence and Mortality

According to the National Cancer Institute, ovarian cancer is the fifth leading cause of cancer death among women in the United States and has the highest mortality rate of all gynecologic cancers. It is estimated that 21,980 new cases of ovarian cancer will be diagnosed in the United States in 2014, and that 14,270 women will die of this disease.

Dr. Greer is the corresponding author for the PLOS ONE article.

Funding for this research was supported by a grant from the American Cancer Society. The study authors reported no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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