Scientists discover protein that stops prostate cancer in its tracks

ST. LOUIS, Mo. — In 2021, about 248,530 U.S. men will receive a prostate cancer diagnosis from their doctor. According to the American Cancer Society, 34,130 will die of the disease. For years, scientists have searched for new methods to slow the spread of cancer. Now, a new study has discovered a protein that halts the progress of prostate cancer.

In experiments, the “super molecule” caused human tumors implanted in mice to shrink. Researchers believe it may help patients who have become unresponsive to hormonal therapies.

“The drugs that we have to treat prostate cancer are effective initially, but most patients start developing resistance and the drugs usually stop working after a year or two,” says study senior author Professor Nupam Mahajan of Washington University School of Medicine in St. Louis in a release.

“At that point, the options available for these patients are very limited. We are interested in addressing this need — developing new therapies for patients who have developed resistance — and we believe the RNA molecule we’ve pinpointed may lead to an effective approach.”

NXTAR may suppress tumors

Genetic molecules in the body called ribonucleic acid (RNA) “translate” instructions encoded in our DNA. About one in eight men will get prostate cancer, making it the most common male cancer. It mainly affects men over 50, with its main driving force being the androgen receptor — a protein that produces testosterone. The newly discovered protein, dubbed NXTAR (next to the androgen receptor), acts as a brake.

“In prostate cancer, the androgen receptor is very clever. Our research shows it suppresses its own suppressor; essentially it binds to NXTAR and shuts it down. This means in all the prostate cancer samples we study, we rarely find NXTAR, because it is suppressed by the heavy presence of the androgen receptor in these types of tumors,” Prof. Mahajan explains.

“We discovered NXTAR by using a drug my lab developed that suppresses the androgen receptor. When the androgen receptor is suppressed, NXTAR starts to appear. When we saw this, we suspected we had discovered a tumor suppressor.”

Nanoparticles could play a key role in treatment

Scientists originally developed the drug, called (R)-9b, to block the androgen receptor. It ended up revealing the presence and role of NXTAR. In lab rodents, restoring its expression caused tumors to decrease in size. What is more, injecting just one small section was sufficient to do the job.

“We are hoping to develop both this (R)-9b drug and NXTAR into new therapies for prostate cancer patients who have developed resistance to the front-line treatments. One possible strategy is to encapsulate the small molecule drug and the key piece of NXTAR into nanoparticles, perhaps into the same nanoparticle, and shut down the androgen receptor in two different ways,” the researcher concludes.

Mahajan has filed a patent application on the (R)-9b drug, licensed to his biotech startup TechnoGenesys.

The findings appear in the journal Cancer Research.

South West News Service writer Mark Waghorn contributed to this report.

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