19
synthesis or AR blocking, or both, reagents. Often, CRPC emerges in the bone metastatic setting,
in which the primary tumor has been removed but bone metastatic deposits develop
29
. Most AR
blockers, including the clinically and widely used bicalutamide and enzalutamide, block the AR
from being activated by its natural ligand DHT, but the effect is transient in nature
30
. In addition,
these compounds are not designed to down-regulate the expression of the AR, which constitutes a
different mode of action. Since ca27 induces such a down-regulation of the AR, leading to cell
death, it represents a relatively new approach towards a potential therapeutic modality. This
warrants further investigation into its mechanism of action. As outlined in our hypothesis, one
possibility is the direct physical interaction between ca27 and the AR,
which could induce its
degradation. Degradation enhancing curcumin analogs have previously been described
31
rendering
this pathway a likely mechanism of action for ca27. Should the present study reveal and suggest
an interaction between ca27 and the AR and should in vitro biophysical and biochemical tests
corroborate
such findings, this will warrant the planning and execution
of pre-clinical studies
utilizing animal models of prostate cancer.
