FIGURE 8.

Schematic illustration of overcoming prostate tumor therapeutic resistance after ADT, and taxane chemotherapy with TGFβ1 signaling blockade. In response to TGFβ1 signaling inhibition, prostate tumor cells undergo EMT to MET conversion, reverting to an epithelial phenotype and glandular re-differentiation while retaining nuclear AR activity. Certain tumor cells may exhibit selective actin cytoskeleton remodeling that would sensitize them to sequential drug action. These tumor cells are now “primed” to be targeted by antiandrogen (sequential to galunisertib treatment) to undergo apoptosis thus driving tumor regression.