Posted 5/12/2016 7:11 PM (GMT 0)
Hi Avis-
Testosterone is the primary signal that tells prostate cells to grow (one cell becomes two cells and so on) and it does so by moving into the cell and attaching to a protein called the androgen receptor (AR). The AR, with testosterone (T) bound, then goes into the innermost part of the cell (the nucleus) where it can attach to DNA and turn on genes that push the cell to divide. Well behaved prostate cells have other internal mechanisms that prevent cell division even when T is available, preventing unwanted growth. Prostate cells that have converted to prostate cancer cells have developed defects in the "stop growth" mechanism, allowing the "go-go-go" signal of T to drive uncontrolled growth.
So initial hormone therapy is based upon denying PCa cells the T that drives their growth, but over time some of the PCa cells develop resistance such that the low T levels (castrate levels) are sufficient to drive growth. These resistance mutations make make AR better at binding T, or they may amplify the number of AR genes in the cell- in either case, this makes a castrate T level capable of triggering cell growth.
Xtandi, Zytiga, and others (like casodex) work to disrupt the binding of T to AR and the transport of AR into the nucleus, hopefully blocking the newly active T signal to grow-
Since most PCa cells make PSA, it can serve as a useful proxy for the growth and appearance of new PCa cells in the body; hence your father's doctor follows that to know if the AR blockers are having an effect, and all of this is independent of the T leve at this point in his journey
rf