Reported that the treatment leads to Change dutasteride median PSA level of 66% at 4 years. The differences in the suppression of the PSA between finasteride and dutasteride may reflect the effects of the blockade of the 5 AR 1 in prostate cells. The PSA is not reduced to zero implies a permanent Estrogen Receptor Pathway bond of testosterone on the androgen receptor, which is normally much lower than the DHT-binding, 24 or the m Possible existence of a type 3 isoenzyme.25 The significance of these data from the results of the Prostate Cancer Prevention Trial, in which the general decline in R ll of prostate cancer with finasteride therapy associated with an increase in prostate cancer coupled with high-quality speakers highlighted.
26 siebenunddrei Ig percent of cancers in the finasteride group had a Gleason score 7-10 pr with over 22% in the placebo group, with increasing high Gleason cancer Sentieren Haupts Normally in the range 8-10. 26 It has been suggested that detection bias for high-grade tumors in patients treated with finasteride, can k Explained Help Ren, these results and that this be d partly due to the specificity of t and sensitivity t the detection of PSA and digital rectal examination under 5 IRA treatment.27 finasteride inhibits only 5 AR2, resulting in a decrease in PSA of 50%. In the low-grade cancer, $ 5 AR2 can still prevail, therefore occurs in both finasteride and dutasteride dinner should have a sufficient reduction in PSA level. However, high quality cancer, concentrations of 5 5 both AR1 and AR2 increased13 that finasteride is theoretically block the progression of cancer with low but not high-quality cancer.
This problem can be stated with the approval of the reduction by dutasteride of prostate cancer events study data.28 The identification and characterization of somatic mutations in the AR 5 prostate cancer tissue in humans has implications for times in the Pr Disposition and progression of prostate cancer. Makridakis et al. reported that in about 60% of prostate tumors, the somatic substitutions occur in the protein coding region of the gene SRD5A2 encoding 5 AR. About 20% of tumor samples had mutations in SRD5A2 clear that activated receptor stero Androgens, w While only 7% had SRD5A2 mutations, the enzymatic activity of t reduces the F Is significant.
It is therefore m Possible that these genetic variants k Can play a r Important in the development and progression of BPH and prostate cancer, and may help to individualize cancer treatment and Pr Prevention of pharmacogenetics mechanisms.29 more in vitro analysis showed that dutasteride is stero potent inhibitor AR 5 for most enzyme variants, with the exception of P48R and F194L and that dutasteride treatment would also be expected, since they pharmacogenetic variation smaller in vivo than finasteride prostate cancer treatment.30 with castration remains a therapeutic challenge, and it has been suggested that dual inhibition may be useful 5 AR in its administration. Eggener and colleagues31 reported that a combination of dutasteride, finasteride, but not more than castration, much larger Ere reduction of tumor growth in LNCaP xenograft Nacktm Mice there castration alone reached and treated M mice were dutasteride for 3 to 5 times h more often than to be alive 70 days after treatment Tre