Prostate cancer growth is regulated by the androgen receptor pathway and so
therapies to block androgen production and action are commonly used for the treatment
of this disease. Although initially successful in the majority of patients, resistance to
hormonal therapy generally emerges and patients’ tumours progress to the ‘castrate
resistant’ phase, for which few therapeutic options exist. Expression of the androgen
receptor is maintained in castrate resistant prostate cancer and there is a significant body
of evidence that demonstrates that the androgen receptor is driving growth, even in the
androgen-depleted environment. Several mechanisms have been described to explain
how the androgen receptor is active under such circumstances and this current review
summarises how mutations of the androgen receptor provide a growth advantage
through mechanisms that may involve cofactor recruitment, reduced ligand specificity
or promoting constitutive activity. Indivividual mutations appear to differentially
regulate gene expression, therefore tumours may behave differently dependent upon
which mutation is present and which ligand is driving growth.
Keywords: Prostate cancer, Androgen receptor, Mutation, Therapy resistance,
Castration resistance, Hormone therapy.