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Possible new way to treat advanced prostate cancer

Researchers from the Pharmacology Department at the Indiana University School of Medicine may have found a future way to cure prostate cancer that metastasizes to the bone.

Theresa A. Guise, MD, and Pierrick G. J. Fournier, PhD from the Center for Scientific Research and Higher Education at Ensenada recently published an article in the journal Cancer Cell that explained how a protein involved in cell signaling pathways promotes bone metastasis in patients with advanced prostate cancer. Dr. Fournier said, “This finding could make a difference in how prostate cancer is treated in the future. The unknown qualities of cancer frequently lead to aggressive treatments that are unnecessary. If we can determine a laboratory test that can serve as an indicator of the likelihood of progression or the severity of the disease, we could make better decisions about treatments and improve the quality of life for many patients.”

Prostate cancer key statistics:

• Prostate cancer is the second most common cancer in American men, other than skin cancer. 

• Prostate cancer is the second leading cause of cancer deaths in men. 

• About 1 in 7 men will be diagnosed with prostate cancer in their lifetime. 

• The average age of diagnosis is 66. 

• Prostate cancer is very rare in men younger than 40, but the risk of developing prostate cancer significantly increases after age 50. About 6 in 10 cases of prostate cancer are found in men over the age of 65.

• It is estimated that in 2015, there will be about 220,800 new cases of prostate cancer diagnosed. 

• African American men are 70 percent more likely to be diagnosed with prostate cancer.

• Having a father or brother with prostate cancer more than doubles a man’s risk of developing the disease. The risk is much higher for men with multiple relatives with a history of the disease.

• Obesity and metabolic syndrome can increase risk by 57 percent; they can also mean increased prostate cancer tumor volume and recovery risks.

• For now, the PSA test is the best way to establish a prostate health baseline; men should have a baseline PSA test starting at age 40.

• Robotic prostate surgery remains a leading treatment option, with highly successful recovery and quality of life results when performed by an experienced surgeon.

The researchers explained that the protein is TGF-beta. This protein is essential to cell functions like growth, proliferation, and death. It is also linked to bone metastases in melanoma and breast cancer. This is the reason why Dr. Guise thought that intervening with the protein TGF-beta may prevent prostate cancer from metastasizing in patients with advanced prostate cancer. 

Another protein, PMEPA1, is seen in high amounts in patients with prostate cancer. Specifically, this protein is seen in their cancerous cells. This encouraged the researchers to come up with a hypothesis regarding the function of this protein in prostate cancer metastasis.

According to Dr. Guise, “Comparing data on patients with prostate or breast cancer, we found those with low amounts of PMEPA1 developed metastases faster and had shorter survival. By inhibiting TGF-beta, we believe we could reduce the spread of prostate cancer to the bone and increase survival.” The researchers tested their hypothesis by performing experiments that are explained in detail in their recent article, “The TGF-β Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone.”

What the researchers found is that the results showed that PMEPA1 is less prevalent in metastatic bone tumors but more prevalent in the cells of patients with prostate cancer. In comparison, the TGF-beta protein is more prevalent inmetastatic bone tumors. In conclusion, the researchers determined that TGF-beta negatively regulates PMEPA1 activity. Therefore, decreasing the activity of TGF-beta may prevent bone metastases in prostate cancer patients. 

Researchers believe that their findings could potentially make a difference in the future of treating advanced prostate cancer that has metastasized to the bone. They believe that PMEPA1 may be used in diagnosing the risk for metastasis in patients with advanced prostate cancer. Furthermore, it could even be used to help identify the survival risk after a man has been diagnosed with prostate cancer. 

Currently, doctors use two diagnostic tools to help diagnose prostate cancer: the Gleason score and the PSA (prostate-specific antigen) test. Using PMEPA1 to help diagnose prostate cancer could be an additional tool used alongside the Gleason score and the PSA test to help determine the prostate cancer stage and as well as the most optimal treatment plan.