In past posts I have suggested that it might be prudent to include Avodart & statin when on ADT. The idea being to block backdoor androgen production. With the recent discussion of treatment-emergent, aggressive PCa variants, it seems like a good time to examine "Androgen Annihilation".
When researchers realized that the androgen receptor [AR] remains in play when ADT fails, it breathed new life into targeting the AR axis. Huggins simply hadn't gone far enough with castration. What was needed was a scorched earth approach (& hopefully the cure wouldn't kill the patient).
'Androgen Annihilation' is self-explanatory. It means total war on the AR. & it implies using multiple drugs - one for each escape route. Perhaps a cure might even be possibe? But at least a durable response? The risk being that a particularly nasty treatment-emergent variant might emerge.
For those interested in the concept, a 2014 paper by James Mohler (Roswell Park) [1] explains it well:
"Androgens may be “annihilated” using simultaneously a luteinizing hormone releasing hormone (LHRH) antagonist or agonist to inhibit testicular production of testosterone, a cytochrome P45017A1 (CYP17A1) inhibitor to diminish metabolism of testosterone via the adrenal pathway and dihydrotestosterone (DHT) via the backdoor pathway, a 5α-reductase inhibitor to diminish testosterone reduction to DHT and backdoor metabolism of progesterone substrates to DHT, and a newer anti-androgen to compete better with DHT for the androgen receptor ligand-binding domain."
-Patrick
