Ovarian cancer is a deadly cancer with few treatments available, and the prognosis is particularly bleak for women diagnosed with certain subtypes. Now, a new study brings fresh hope in the form of a new treatment target for a particularly aggressive form of the disease.
There are several subtypes of ovarian cancer - depending on the type of tissue and cells involved. One of these is ovarian clear cell carcinoma, which affects up to 10% of ovarian cancer patients in the US and about 20% of patients in Asia.
While ovarian cancer patients initially respond to standard platinum-based chemotherapy, the response rate for those with ovarian clear cell carcinoma is typically poor and, unfortunately, there are currently no effective alternative therapies.
Researchers at the Wistar Institute in Philadelphia, PA, hope their discovery will pave the way to much-needed treatments.
Their study, published in the journal Nature Medicine, takes ovarian cancer into a growing new area of cancer treatment - personalized therapy.
'A target for effectively halting the progression of ovarian cancer in a personalized manner'
Corresponding author Rugang Zhang, an associate professor in Wistar's Gene Expression and Regulation Program, says their study offers a target for effectively halting the progression of ovarian cancer in a personalized manner, depending on the patient's genetic makeup. He adds:
- Ovarian cancer causes more deaths than any other cancer of the female reproductive system
- The vast majority of women who get ovarian cancer are middle-aged and older
- Early detection is key to treatment success.
"For patients with this particular subtype [ovarian clear cell carcinoma], this newly discovered targeted approach may eventually lead to the first effective targeted therapy they've ever had."
Prof. Zhang and colleagues studied a chromatin remodeling gene called ARID1A, which has been implicated in a number of cancers.
ARID1A allows chromatin - a protein structure that packs DNA tightly inside cells - to open up so cells can receive signals that tell them what to do. This is important for stopping them becoming cancerous.
Recent studies have shown that ARID1A is mutated in over half of patients with ovarian clear cell carcinoma; in fact, the gene has one of the highest mutation rates among all types of cancer.
Inhibiting EZH2 in ovarian cancer patients with mutated ARID1A
In this new study, the team focused on the interaction between mutated ARID1A and EZH2 - an enzyme that helps to compact DNA in the chromatin structure. When this interaction occurs, it appears that genes in the compacted regions are switched off, which in turn stops the DNA instructions necessary for making tumor-fighting proteins from passing to the protein-making machinery.
While normal cells require a certain level of EZH2, too much of the hormone has been linked to the progression of a number of cancers, including ovarian clear cell carcinoma.
The study explored the possibility of inhibiting EZH2 as a cancer treatment for patients with a mutation in the ARID1A gene. The researchers confirmed this might be a promising way forward when they showed ARID1A-mutated ovarian cancers are sensitive to EZH2 inhibition.
The highlight of the study came when the team discovered blocking EZH2 resulted in regression of ovarian tumors with mutated ARID1A. This did not affect ovarian tumors with normal or unmutated ARID1A.
The team concludes:
"Our data indicate that pharmacological inhibition of EZH2 represents a novel treatment strategy for cancers involving ARID1A mutations."
The researchers believe their findings will have far-reaching implications and note that EZH2 inhibitors are currently in clinical development.
Funds for the study came from a number of sources, including the National Institutes of Health, the Department of Defense and the Ovarian Cancer Research Fund.
Last month, Medical News Today reported another study published in the journal Nature Communications, where using a new mouse model of ovarian cancer, researchers found too little expression of ARID1A and too much expression of another gene called PIK3CA always resulted in the mice developing ovarian clear cell carcinoma.