Can an RNA Molecule Keep Prostate Cancer From Growing?
Using mice implanted with human prostate tumor samples, researchers at Washington University School of Medicine zeroed in on an RNA molecule that keeps prostate tumors from growing.
Not every cancer is a death sentence. In fact, survival rates from all forms of the disease are improving. The two most common forms for men, skin and prostate, are often easily treated. Unfortunately, some prostate cancer is aggressive and fast-growing. Drug therapies often become ineffective by the second year. Recently, researchers discovered a way to combat this. How did they do it and what does it mean for men battling the disease?
A Very Common Cancer
Part of the male reproductive system that includes the penis, testicles, and seminal vesicles, the prostate rests in front of the anus and below the bladder. This walnut-sized gland is responsible for producing seminal fluid (which feeds and transports sperm). As men age, their prostate often gets bigger which may narrow the urethra and affect their urination. However, this benign prostatic hyperplasia is not cancer.
Like all cancers, prostate cancer occurs when genetically damaged cells continue to divide and multiply rather than die off. With prostate cancer, a protein called the androgen receptor binds to testosterone and stimulates the growth of tumors. These tumors often grow extremely slowly and without any noticeable symptoms. Because they most commonly occur in men over the age of 50, there’s a decent likelihood that they will die of other causes before prostate cancer becomes a concern. Indeed, an estimated one out of eight men will be diagnosed with prostate cancer in their lifetimes. Over three million men in the U.S. are still alive despite having received this diagnosis at some point. Every year over a quarter of a million men learn they have prostate cancer.
Yet while it’s survivable for most, for some the disease is fatal. Other than lung cancer, it kills more men than any form of the disease. Over 34,500 men in the U.S. die from the disease each year. The risk increases when the cancer metastasizes or spreads. Because the average age of a prostate cancer patient is 66, the issue for many is whether a debilitating course of aggressive treatment is worth it. Options include radiation, chemotherapy, surgery, and drugs. However, as Nupam P. Mahajan, PhD, a professor of surgery in the Division of Urologic Surgery at Washington University School of Medicine in St. Louis points out, “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. 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.” To do that, Mahajan‘s team looked at an RNA molecule that could hold the key to prostate cancer’s spread.
Using mice implanted with human prostate tumor samples, researchers at Washington University School of Medicine zeroed in on an RNA molecule that keeps those tumors from growing. Called a long noncoding RNA, the molecule was discovered while they were looking at the DNA holding codes for the androgen receptor––the cancer-stimulating protein. Just beside this, they found DNA producing the long noncoding RNA molecule. After determining that it plays a role in regulating the cancer-stimulating protein, they began developing a drug that would restore the abilities of the long noncoding RNA to shut down the androgen receptor in men with prostate cancer. They called this long noncoding RNA NXTAR because it was found next to the androgen receptor.
“In prostate cancer, the androgen receptor is very clever,” explains Mahajan. “Our research shows that it suppresses its own suppressor; essentially it binds to NXTAR and shuts it down. This means that in all the prostate cancer samples that we study, we rarely find NXTAR, because it is suppressed by the heavy presence of the androgen receptor in these types of tumors. We discovered NXTAR by using a drug that my lab developed that suppresses the androgen receptor. When the androgen receptor is suppressed, NXTAR starts to appear. When we saw this, we suspected that we had discovered a tumor suppressor.”
While it is still in early stages, the research is promising for men for whom drug therapy is no longer working.