A study conducted at Georgia State University and the University of Georgia gives us novel insight into the chemoresistance of ovarian cancer and offers a potential therapeutic approach to overcoming it. Inhibiting enzymes that lead to changes in gene expression could decrease chemotherapy resistance in ovarian cancer patients, researchers say. Dr. Susanna Greer and her colleagues have identified two enzymes that suppress proteins that regulate cell survival and chemoresistance in ovarian cancer.
Ovarian cancer is the deadliest of all gynecologic cancers with a mortality rate of 60% for the 1 in 72 women estimated to be at risk for this disease in their lifetime. Because it can develop a resistance to chemotherapeutic drugs over time, the high mortality rate of ovarian cancer persists to this day. Typically, the cancer will respond to initial treatment but then grow resistant; understanding the biological mechanisms that underlie this acquired resiliency could help improve treatment and save lives.
In a previous study, these researchers found that the expression of the protein that regulates ovarian cancer cell growth and survival – RGS10 – was suppressed in chemoresistant cancer cells. The suppression was caused by two mechanisms, DNA methylation and histone deacetylation. In the current study, the research team focused on the epigenetic regulation of RGS10 expression to investigate how ovarian cancer might acquire this resistance to chemotherapy.
They identified two important epigenetic regulators: HDAC1, a histone deacetylase, and DNMT1, a DNA methyl transferase. When they decreased the expression and blocked the activity of HDAC1 and DNMT1, there was a significant increase in RGS10 expression and cell death. This also decreased the binding of HDAC1 to RGS10 in chemoresistant cells.
These findings indicate that inhibiting HDAC1 and DNMT1 modulates RGS10 expression, thereby decreasing ovarian cancer chemoresistance. Potential therapeutic approaches that focus on inhibiting these enzymes may help combat the resiliency of this deadly and prevalent cancer.
Source: Learn all about it and read more about their findings here: Inhibition of HDAC1 and DNMT1 Modulate RGS10 Expression and Decrease Ovarian Cancer Chemoresistance. Cacan E, Ali MW, Boyd NH, Hooks SB, Greer SF.
1) Ovarian Cancer National Alliance. 2014.
2) Georgia State University. Decreasing chemoresistance in ovarian cancer. ScienceDaily. May 2014.