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Post by Allen on Jul 29, 2014 22:45:44 GMT -8
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Post by Allen on Sept 3, 2014 18:30:40 GMT -8
One of the de-methylators, Azacitibine, has been demonstrated to reverse docetaxel resistance in a pilot study. Only about half of men with mCRPC have a significant PSA response (>50%) to docetaxel. Resistance eventually emerges, with everyone experiencing progression within 3 years. Now, cabazitaxel (Jevtana) is a second-line chemo defense after docetaxel failure. Still, we would like to be able to keep docetaxel working. This study identified a few men who suffered disease progression while taking docetaxel. They were given a weekly cocktail of azacitibine + docetaxel + (filgastrim to prevent febrile neutropenia). More than half had a significant PSA response, and 30% had measurable cancer regression. This kind of DNA repair may keep docetaxel working longer. Phase I/II Study of Azacitidine, Docetaxel, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Therapy
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Post by Allen on Sept 4, 2014 16:36:41 GMT -8
I asked Dr. Rakesh Singal, the lead author of the above study, about his plans for a future clinical trial. He replied:
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Post by robertc on Sept 5, 2014 12:30:58 GMT -8
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Post by Allen on Sept 5, 2014 14:44:15 GMT -8
Certainly. As you can read there, Vidaza is mentioned. Epigenetics refers to anything that turns on or off existing genes. Methylation of DNA often occurs with age or as a result of transcription errors as the gene replicates, and often happens in cancerous cells which replicate frequently. These 5-AZA de-methylators will fix some of the methylated DNA.
It looks like research in this potentially fruitful area is on hold for now :-( However, oncologists may be using them for PC anyway.
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Post by Allen on Sept 9, 2014 9:59:17 GMT -8
The following study found that methylation of 3 specific genes is highly prognostic for PC mortality. The authors suggest that their detection should be added to Gleason score and PSA in determining PC risk. If an assay becomes widely available and affordable, it identifies a sub-group with whom de-methylator therapy may be beneficial. Methylation prognostic for PC Mortality.pdf (1.24 MB)
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