ATR and posterior cortical atrophy: In recent years, our lab has identified a key role for the DDR kinase, TLK1, in mediating key aspects of adaptation to ADT, first by promoting a cell cycle arrest (through the TLK1>NEK1>ATR>Chk1 kinase cascade) under the unfavorable growth conditions (androgen deprivation), and then by reprogramming the PCa cells to adapt to androgen-independent growth via the NEK1>YAP/AR>CRPC conversion.