Why Prostate Cancer Patients Fail Hormone Deprivation Therapy.

[George A. Brown]

My Us Too Suport Group Leader passed on excerpts of the following article to the Group:

Johns Hopkins scientists identify receptor type that makes cancer cell resistant to therapy, more agressive; Release Date 31 Dec 2008. Further Information go to www.urology.jhu.edu/

Using a large database, the researchers searched for variations of the nucleic acid RNA that prostate cells use to create androgen receptors, eventually identifying seven RNA sequences different from the "normal" androgen receptor already known to scientists. When they looked for these sequences in cells isolated from 124 prostate cancer patients, they found over-production of these outlaw variants in prostate cancer cells from patients whose disease had become resistant to hormone deprivation therapy. One variation known as AR-V7, was also prevalent in a select group of patients who had never taken hormone therapy, but whose cancers aggressively regrew after surgery to remove their tumors.

To see how androgen receptors made frow AR-V7 differ from others, the researchers forced lab-grown prostate cancer cells to produce only the AR-V7 sequence. Unlike cells with other androgen receptors, those with only AR-V7 receptors acted as if they were continually receiving androgens, turning on at least 20 genes that rely on androgens for activation, even though no androgens were present.

The results suggest that hormone therapy might encourage prostate cancer cells to overproduce the AR-V7 receptors over time, leading them to survive and grow agressively even without androgens, explains Luo. In some patients, he adds, AR-V7 receptors might already be prevalent even without hormone therapy, predisposing them to an already-agressive form of prostate cancer that woun't respond as well to hormone deprivation therapy.

"We may eventually be able to develop an assay to test for this androgen receptor varient, giving us a way to test which patients are good candidates for hormone deprivation therapy and providing a way to monitor disease progression in patients already on this therapy" lou says.

Examining the differences between AR-V7 and other androgen receptor varients may also provide researchers with new ideas to develop prostate cancer-fighting pharmaceuticals, he adds

[E. Michael D. ("Mike") Scott]

George:

A small point but critical to many people's perspectives ... Prostate cancer patients don't "fail hormone deprivation therapy." On the contrary, the truth is that hormone deprivation therapy fails many prostate cancer patients (in the end)!

Mike

[George A. Brown]

Mike, I think that is a critical perspective, good point.

[RayAnthony]

Your probably right, but I wish I had not read that! Maybe I have my head in the sand, or somewhere else!!

[donald rappaport]

Well my drug store has had a guy coming in for 5 years for LUPRON. Not bad for starters.
Don

[Ralph Valle]

The implication of the study is that androgen deprivation drives androgen independence. If such is the case, how to explain those cases in which the cancer doesn't respond to deprivation because it developed androgen independence BEFORE the therapy was applied?

How to explain the fact that many men do not become androgen independent while on ADT and in fact the therapy has demonstrated a slight survival benefit?

The success of androgen deprivation depends on the tumor status (as far as androgen dependence/independence of the tumor load). If the balance is towards dependence, long responses are typical. In the opposite case, poor responses are the norm. This is one of the reasons that early therapy is preferable.