Discovery of ovarian cancer target paves way for new treatment strategy

Date: Feb-17-2015Ovarian 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.

Inhibiting an enzyme in ovarian cancer patients with a particular gene mutation could potentially halt the cancer.

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:

Fast facts about ovarian cancer

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.

Learn more about ovarian

cancer

"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.

Written by Catharine Paddock PhD

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.