Several lines of evidence suggest that androgen dependent AR signaling remains functional in CRPC. It is known that the serum in medical CRPC is never absolutely androgen free, that recurring androgens can be found within the prostate at levels able to activating the AR despite castration and that enhanced intratumoral androgen synthesis is commonly observed in CRPC. Moreover, 50% of CRPC patients Lonafarnib 193275-84-2 showing disease progression on lines of hormonal treatments remain responsive to further hormone manipulation, indicating that androgen dependent AR function remains in CRPC. Consequently, AR activity in CRPC is assessed largely depending on androgen responsive reporters or prostate-specific androgen production. Next-generation drugs have qualified androgen dependent AR signaling by inhibition of androgen synthesis and block of AR ligand binding. But, the heterogeneous and frequently temporary response to these new anti androgen solutions raises the issue of how and whether AR mediated gene transcription occurs in the absence of ligand binding. Prostate cancer Endosymbiotic theory is just a molecularly heterogeneous illness even within a single patient, and multiple mechanisms may possibly co ordinately bring about CRPC progression. While ligand dependent AR signaling continues to play an important part in the early stages of CRPC when residual androgen mediated AR signaling is active, ligandindependent activation of AR may occur in an atmosphere where androgen levels are below castrate levels following significant ligand depriving treatments. Such treatments have been related to complete elimination of testosterone within the cyst microenvironment and in some cases a loss of CYP17 in prostate cancer cells. More importantly, the fact all anti androgen methods ultimately fail strongly Ganetespib cost demonstrates the necessity to identify and target alternative androgen independent AR signaling pathways. . We reason that androgen dependent and androgen independent AR signaling may coexist, and that the relative importance of these two pathways depends upon local androgen levels, AR expression and other cellular contexts including co specialists. The androgen independent AR binding described here occurs at exceptionally low levels of androgen, which might provide a system for CRPC to develop and survive in a truly androgen free milieu. AR binding events have been identified by previous studies in the presence of androgen in CRPC cells. In this research, we executed AR ChIP seq in CRPC cells cultured in hormone depleted media and identified a significant number of strong androgen independent AR binding events. Taken together, these results show that both androgen dependent and independent AR signaling play a role in CRPC. The identification of androgenindependent AR binding activities does not diminish the significance of androgen-dependent AR signaling.