The transcription factor RUNX1 marks a distinct lineage of luminal castration-resistant prostate cells established early during development and enriched in the periurethral region of adult mouse prostate.
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.
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.
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.
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.