Researchers Find RNA Molecule That Suppresses Prostate Cancer

Cancer uses different mechanisms to grow, spread and become resistant to treatment, one of which is shutting down molecules within the cell that suppress cancer.

"Our DNA contains genes coding for proteins that suppress cancer or tumor formation in various organs," said S. Adam Ramin, M.D., a urologic surgeon and the medical director of Urology Cancer Specialists in Los Angeles. "These genes are called tumor suppressor genes. When tumor suppressors are turned off, there is a higher likelihood of tumor formation and progression of cancer to higher stages. Many cancers, including bladder and prostate, progress because of the loss of the tumor suppressor genes."

Researchers from the Washington University School of Medicine in St. Louis identified both a novel RNA molecule—tagged NXTAR—that suppresses prostate cancer and a way to restore it. (RNA stands for ribonucleic acid.) They conducted experiments in prostate cancer cells and in mice implanted with human prostate cancer grafts. Their findings were published in the Cancer Research journal.

What does the study show?

"RNA is a critical component in all living cells which does a broad range of functions. There are different types of RNAs," explained Asit Paul, M.D., Ph.D., an associate professor of medicine and a medical oncologist at Virginia Commonwealth University's Massey Cancer Center in Richmond. "One of the well-recognized functions of RNA is to carry instructions for protein synthesis. There are also noncoding RNAs, which do not encode protein but control various regulatory signals in a cell. The role of noncoding RNAs in cancer growth and progression is an emerging field of research."

Androgen receptor signaling is critical for prostate cancer growth. Paul said the study's researchers showed that "NXTAR, a novel noncoding RNA, suppresses the expression of the androgen receptor gene in prostate cancer cells, and restoring NXTAR can be a strategy to develop treatment for hormone-resistant prostate cancer."

"By being able to turn on this RNA, it is possible to actuate production of the tumor suppressor proteins, which then can suppress further prostate cancer formation," Ramin added.

How useful can NXTAR be for treatment?

Paul said the study provides new insight into the process at both the cellular and molecular levels through which prostate cancer cells develop resistance to an effective medication.

"If the mechanisms and mediators of resistance are understood, these can be exploited to develop novel treatment to overcome them," Paul explained. "This knowledge is essential in new drug development, such as small-molecule inhibitors for treatment of resistant prostate cancer."

This ability to manipulate RNA that codes for tumor suppressor genes is relatively new in science and medicine, Ramin said. This particular pathway, theoretically, is an excellent and promising method to treat more advanced cases of cancers, including prostate cancer.

The future of this novel research

Androgens, specifically the testosterone hormone released by the testes, stimulate the growth of prostate cancer. Suppression of testosterone by medication or the removal of the testes is the mainstay of treatment for advanced prostate cancer, Paul explained. This strategy is effective initially, but some patients develop resistance.

"Cancer cells become resistant to hormone suppression alone over time. Hormone-resistant prostate cancer is a fatal disease, and there is a critical need for new drugs to improve the outcome," he said, adding that several new-generation medications which block androgen receptors in tumors or inhibit the synthesis of androgen hormones are now available.

"These new drugs improve outcomes, but patients with prostate cancer also become resistant to these new medications over time," Paul added. "The understanding of the molecular mechanism of resistance is, therefore, essential to develop new drugs targeting the resistance mechanism. This study identifies that restoring this long noncoding RNA could be one strategy to treat hormone-resistant prostate cancer."

Ramin said further studies are needed to determine how to control the RNA translation. Furthermore, scientists need to devise a system to deliver the drug that controls this particular RNA.

"This indicates that we are still a few years behind in reaching this particular target as a therapeutic measure against prostate cancer," Ramin said.