Prostate cancer affects the male prostate, an organ responsible for the production of seminal fluid and the transport of sperm. Prostate cancer is caused by abnormal prostate-cell growth, which leads to the formation of a malignant tumor. Prostate cancer is one of the most common male cancers, with approximately 24,000 Canadian men diagnosed each year. Symptoms of this disease include erectile dysfunction, difficulty urinating and pelvic pain. In its early stages, prostate cancer is highly curable. When advanced, abnormal prostate-tumor cells travel from the prostate to other organs, including the lung, liver, adrenal glands, lymph nodes and bone. Malignant cells can populate these locations, forming secondary tumors. This secondary tumor formation is termed metastasis. When prostate cancer is metastatic, patient morbidity and mortality increases. Identifying proteins involved in prostate cancer metastasis may elucidate effective treatment options.
Several genes have been implicated in the development of prostate cancer, however, the specific proteins involved in the formation of metastatic disease are unknown. Faltermeier and colleagues obtained metastatic prostate cancer samples from over 150 patients. They found that approximately 10% of these samples had mutated BRAF and CRAF kinase activity. These are proteins responsible for the chemical modification of other proteins. This discovery led the authors to conclude that mutated kinase activity potentially drives some forms of prostate cancer metastasis. However, what are the roles of un-mutated kinases in prostate cancer metastasis? What molecular mechanisms account for the other 90% of patient disease? The authors found that un-mutated kinases ARAF, MERTK and NTRK2 were overexpressed in 69%, 33% and 32% of diseased tissues respectively. Interestingly, these kinases were not highly expressed in early-stage prostate cancer samples and likely play an important functional role in the induction of metastatic prostate disease.
The research of Faltermeier and colleagues outlines several kinases involved in the development and progression of prostate cancer. The implications of this research are far-reaching and multi-disciplinary. Extrapolating the findings of this research may lead to novel prostate cancer drug development, in which specific mutated and un-mutated kinase activity is inhibited. Understanding the protein players of prostate cancer has the potential to prevent metastasis, dramatically improving prostate cancer patient survival rates and quality of life.