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He discussed that residual prostate androgens remain after a variety of endocrine manipulations. A ""GnRH"" antagonist given to patients resulted in a castrate level in 24 hours and greater reductions of testosterone and DHT in prostate tissue. This response is heterogeneous among individuals at the gene and protein levels. Analysis of neoadjuvant ADT radical prostatectomy tissue demonstrated that most genes examined are still active at the transcript and protein levels after 3-6 months of ADT. Using tissue from the rapid autopsy program, patients with untreated CaP have levels above the castrate level, but a significant number of metastatic castrate-treated patients do as well.
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Dr. Nelson pointed out that between 2-10 years following androgen-deprivation therapy (ADT) androgen-independent (""AICaP"") clones will develop. This is partially due to mechanisms independent of androgens, with up to 5 pathways identified. These concepts work under the presumption that androgen levels have been adequately suppressed. However, clinically the meta-analysis of combined androgen blockade does demonstrate a small survival benefit using an anti-androgen.
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The protein, named ""Ack1"", is a member of the tyrosine kinase gene family. ""Ack1"" exerts its effect on the reemergence of the cancer by biochemically altering the now inactive androgen receptor in the nucleus of prostate of cells, according to a series of experiments conducted by lead author Dr. Nupam P. Mahajan, assistant professor of pharmacology, and other Lineberger scientists. The kinase activates the receptor via phosphorylation by adding a phosphate group to this protein molecule.
Earp noted that until now scientists haven't completely understood what that conversion means. "Our experiments show that this heretofore understudied protein ""Ack1"" may be crucial in at least a portion of these tumor recurrences. Nupam's study nails down the mechanism by which that conversion happens."
The researchers noted that approximately one-third of androgen-independent human prostate tumors contain an activated ""Ack1"" molecule. "The study is telling us this is a target for therapy and perhaps a very important target for therapy," Earp said.
Earp noted that until now scientists haven't completely understood what that conversion means. "Our experiments show that this heretofore understudied protein ""Ack1"" may be crucial in at least a portion of these tumor recurrences. Nupam's study nails down the mechanism by which that conversion happens."
The researchers noted that approximately one-third of androgen-independent human prostate tumors contain an activated ""Ack1"" molecule. "The study is telling us this is a target for therapy and perhaps a very important target for therapy," Earp said.
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Earp noted that until now scientists haven't completely understood what that conversion means. "Our experiments show that this heretofore understudied protein Ack1 may be crucial in at least a portion of these tumor recurrences. Nupam's study nails down the mechanism by which that conversion happens."
The researchers noted that approximately one-third of androgen-independent human prostate tumors contain an activated Ack1 molecule. "The study is telling us this is a target for therapy and perhaps a very important target for therapy," Earp said.
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"Our new data indicate that picoplatin can be safely combined with established cancer therapeutics. In 66 patients treated up to 10 months, we have observed reversible myelosuppression that is non-cumulative and has not led to any treatment-related mortality," said Jerry ""McMahon"", Ph.D., chairman and CEO of Poniard. "These Phase 1 studies have explored different doses of picoplatin and different dosing schedules either in combination with docetaxel for prostate cancer or with 5-fluorouracil and leucovorin for colorectal cancer. We anticipate that the Phase 2 trials for both indications will begin in the third quarter of 2007, shortly after the maximum tolerated doses have been defined."
