The primary cause of prostate cancer could be the fusion of two genes and the subsequent abnormal prostate cell growth that results when receptors for the hormone androgen get blocked, a new study reveals.
The implication is that standard efforts to treat the disease by targeting the androgen receptors might be missing the real “smoking gun,” a University of Michigan Comprehensive Cancer Center team suggests.
“We need to begin to think about targeting prostate cancer by targeting the gene fusion, and not confining our approaches to androgen receptors,” study author Dr. Arul Chinnaiyan, director of the Michigan Center for Translational Pathology, said in a news release. “If we’re going to find a more durable therapy, we need to get at the gene fusion.”
Chinnaiyan and his colleagues report their findings in the May 18 issue of Cancer Cell.
The authors note that typical prostate cancer treatments focus on drugs that attempt to slow production of androgen, the male hormone that regulates healthy prostate growth. However, such efforts usually become less effective over time as cancer cell resistance mounts, making recurrent cancer much less amenable to similar treatments.
But having earlier identified a so-called “on switch” for prostate cancer development in the form of the initial fusion of a prostate gene with a cancer-causing gene, Chinnaiyan and colleagues now have launched a new investigation into what happens post-fusion.
By using high-tech genetic mapping techniques, the research team found that once fusion takes place, androgen receptors get blocked, in turn cutting off normal prostate cell growth while permitting cancer to spread.
“Our study shows the underlying problem in prostate cancer is the presence of a gene fusion, not the androgen receptor,” Chinnaiyan said in the news release. “In many contexts, androgen signaling is actually a good thing, but the presence of the gene fusion blocks androgen receptor signaling, which alters normal prostate cell development. While current treatments for advanced prostate cancer are focused on hormone deprivation and are quite effective, at least initially, future therapies need to be developed that target the prostate cancer gene fusion.”
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