Analyses of genetically engineered mouse models reveal the androgen receptor-independent properties of a luminal stem/progenitor cell in the prostate epithelium, and its ability to serve as a cell of origin for castration-resistant prostate cancer.
A positive feedback loop between the androgen receptor and a key pentose phosphate pathway enzyme, 6PGD, in prostate cancer promotes tumour cell proliferation, survival and intracellular redox control.
Coregulators mediate selective interactions between DNA-bound androgen receptor and other transcription factors, which control distinct prostate cancer biology, suggesting disruption of critical interactions in these complexes as a novel therapeutic strategy.
Prostate cancer cells maintain heterogeneous androgen receptor transcriptional activity through upregulation of AR-regulated coactivator GREB1, and cells with high activity rapidly develop resistance to antiandrogen therapy in a GREB1-dependent manner.
The transcription factor ERG recruits the PRMT5 enzyme to methylate the androgen receptor, presenting a post-translational regulatory mechanism that could be therapeutically exploited to control cell proliferation.
A mechanistic link between TLE3 loss and glucocorticoid receptor-mediated androgen receptor inhibitor resistance supports the rationale to target GR during anti-hormonal treatment in castrate-resistant prostate cancer.
Mutagenesis studies identified an androgen receptor mutation that converts enzalutamide-a drug recently approved for the treatment of advanced prostate cancer-into an androgen receptor agonist, and modeling studies informed the design of novel drugs that are effective against the mutant receptor.
Prostate cancer resistance to androgen receptor antagonist therapy occurs by way of tumors impeding local glucocorticoid metabolism and inactivation and thereby permitting sustained glucocorticoids to stimulate up-regulated glucocorticoid receptor.