Cancer is crafty. When one avenue driving its growth is blocked by drugs targeting that path, the malignancy often creates a detour, finding an alternative route to get around the roadblock.
In a study at UCLA's Jonsson Comprehensive Cancer Center, researchers found that when a common type of prostate cancer was treated with conventional hormone ablation therapy blocking androgen production or androgen receptor (AR) function which drives growth of the tumor the cancer was able to adapt and compensate by activating a survival cell signaling pathway, effectively circumventing the roadblock put up by this treatment.
The findings could have important clinical implications as this type of prostate cancer, in which the PTEN tumor suppressor gene is inactivated, accounts for about 40 to 50 percent of primary prostate cancers and 70 to 90 percent of cancers that become resistant to hormone therapy, called castration resistant prostate cancers. Based on this study, these prostate cancers could be more effectively treated using a combination of drugs that target the AR cell signaling pathway and the compensating survival pathway, called the PI3K/AKT/mTOR pathway, said study senior author Dr. Hong Wu, a professor of molecular and medical pharmacology and a Jonsson Cancer Center researcher.
The study appears in the June 14, 2011 of the peer-reviewed journal Cancer Cell.
"The most significant take home message from this study is that certain prostate cancers can resist androgen deprivation therapy by activating an alternate pathway to drive its growth," Wu said. "We found that these two pathways are talking to each other, almost like regulatory circuitry, and helping each other get around attempts to kill the cancer. When we suppress one of these pathways, it essentially feeds the other."
Wu characterized the findings as surprising. What they discovered, she said, bucked conventional wisdom about the way PTEN negativ
|Contact: Kim Irwin|
University of California - Los Angeles Health Sciences