Protein that ‘stops prostate cancer in its tracks’ discovered by scientists

Prostate cancer is the most common male cancer and mostly affects those over 50

Mark Waghorn
Friday 05 November 2021 15:30
<p>When the protein was injected into mice implanted with human tumours, it caused the tumours to shrink </p>

When the protein was injected into mice implanted with human tumours, it caused the tumours to shrink

A protein that is said to be able to stop prostate cancer in its tracks has been discovered by scientists. In experiments, the ‘super molecule’ caused human tumours implanted in mice to shrink. It could be given to patients who have become unresponsive to hormonal therapies.

Senior author Professor Nupam Mahajan, of Washington University School of Medicine, St. Louis, said: “The drugs 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.

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

Genetic molecules in the body called RNA (ribonucleic acid) ‘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 over 50s. It is driven by the androgen receptor, a protein that produces testosterone. The newly discovered protein, dubbed NXTAR (next to androgen receptor), acts as a brake.

Prof Mahajan explained: “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 tumours.

“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 tumour suppressor.”

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

Added Prof Mahajan: “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 frontline 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.”

More than 52,000 men in the UK are diagnosed with prostate cancer each year. The disease claims around 12,000 lives annually.

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

The study is published in the journal Cancer Research.


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