Among men worldwide, prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths. As the world's population ages, the number of prostate cancer patients is expected to increase, with an additional 2.4 million newly diagnosed patients and 712,000 deaths annually by the year 2040. But scientists may have identified a novel treatment approach for this deadly cancer.
Reporting in Nature Genetics, researchers have found genetic mechanisms that underlie a cellular transition, in which prostate cancer cells become more aggressive. These particularly harmful cells drive a form of disease known as neuroendocrine prostate cancer (NEPC). This transformation happens in around 20% of advanced prostate cancer patients, leading to the rapid progression of disease that cannot be treated effectively.
In this study, the researchers developed a three-dimensional map of how the structure of compacted DNA changes to activate novel genes during this cellular transformation. Two proteins are generated, called FOXA2 and NKX2-1 that are crucial to this process. FOXA2 makes certain regions of DNA accessible, which allows NKX2-1 to initiate a new process to genetically reprogram the cells and change their identity. Certain enzymes known as CBP and p300 were also found to be critical to this transition.
These discoveries can offer new opportunities to halt this deadly cellular change. The investigators also showed that certain drugs that inhibit the CBP and p300 enzymes could stop the growth of NEPC tumors in research models. More work will be needed to determine if this method is safe and effective, but this approach could also work in humans.
"Prostate cancer is one of the most commonly diagnosed cancers, affecting countless patients and families," said co-correspnding study author Jindan Yu, MD, Ph.D., a professor of urology in the Emory School of Medicine. "While it often responds well to hormone therapy, many cases eventually develop resistance. One major pathway leading to treatment failure and disease progression is the transformation of prostate tumor cells into NEPC, a new beast that lacks the targets for existing prostate cancer drugs."
Sources: Emory University, Nature Genetics