Two genes work together to drive the most lethal forms of prostate cancer, according to new research from the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center (CUMC). These findings could lead to a diagnostic test for identifying those tumors likely to become aggressive and to the development of novel combination therapy for the disease.
The two genes—FOXM1 and CENPF—had been previously implicated in cancer, but no prior study suggested they might work synergistically to cause the most aggressive form of prostate cancer. The study was published online in Cancer Cell.
Using one of the world’s largest supercomputers in cancer research, based at CUMC, the analysis identified FOXM1 and CENPF as a synergistic driver pair in aggressive prostate cancer in both mice and men. Individually, the aberrant expression of these genes does not activate these programs. When acting together, however, the two genes can wreak havoc in the cancer cell and turn it into a very aggressive tumor.
To validate the roles of FOXM1 and CENPF, the researchers silenced the expression of the genes in four human prostate cancer cell lines, first individually and then together. Silencing either gene alone had only a modest effect on the ability of the cells to form tumors. However, co-silencing both genes at once completely stopped the growth of tumors in a mouse.
The researchers then analyzed prostate cancers from a group of more than 900 patients who had undergone prostate removal surgery. This analysis showed a striking correlation between the co-expression of FOXM1 and CENPF and the poorest disease outcome. In contrast, expression of either gene alone did not correlate with aggressive disease. Tumors in which neither gene was aberrantly expressed had the best prognosis. Read the study abstract.
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