Prostate cancer that metastasizes to the bone may be curable in the future using new research from the Pharmacology Department at Indiana University School of Medicine. Theresa A. Guise, MD, and her collaborator at the Center for Scientific Research and Higher Education at Ensenada, Pierrick G. J. Fournier, PhD, recently authored an article in Cancer Cell that explained how a protein involved in cell signaling pathways promotes bone metastasis in patients with advanced prostate cancer.
“This finding could make a difference in how prostate cancer is treated in the future,” said Dr. Fournier, in a news release from the university. “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.”
The protein is TGF-beta, which is integral to cell functions such as growth, proliferation, and death. It is also associated with bone metastases in breast cancer and melanoma, which is why Dr. Guise thought that interfering with TGF-beta may prevent metastasis in advanced prostate cancer patients.
Prostate cancer patients also show high levels of another protein, PMEPA1, in their cancerous cells, prompting the research team to hypothesize a role for PMEPA1 in prostate cancer metastasis. “Comparing data on patients with prostate or breast cancer, we found those with low amounts of PMEPA1 developed metastases faster and had shorter survival,” said Dr. Guise. “By inhibiting TGF-beta, we believe we could reduce the spread of prostate cancer to the bone and increase survival.” To test this hypothesis, the team conducted experiments that are described in their recent article, “The TGF-β Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone.”
Their findings showed that PMEPA1 is less common in metastatic bone tumors but abundant in prostate cancer cells taken from patients. In stark contrast, TGF-beta is high in tumors that metastasize to bone. They concluded that TGF-beta negatively regulates PMEPA1 activity, and reducing TGF-beta activity may prevent bone metastases.
To use these findings, the researchers believe that PMEPA1 may be used in diagnostics for prostate cancer metastasis risk. It may even be used to help determine the chance of survival following a diagnosis of prostate cancer. This tool could be added to the Gleason score and PSA counts that physicians already use to stage prostate cancer to determine the best treatment option. It would help the 220,800 new prostate cancer patients that are diagnosed each year and reduce the 27,540 deaths that occur as a result of prostate cancer each year.
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