TY - JOUR
T1 - Mechanisms of androgen receptor activation in castration-resistant prostate cancer
AU - Sharifi, Nima
PY - 2013/11/1
Y1 - 2013/11/1
N2 - Systemic treatment of advanced prostate cancer is initiated with androgen deprivation therapy by gonadal testosterone depletion. Response durations are variable and tumors nearly always become resistant as castration-resistant prostate cancer (CRPC), which is driven, at least in part, by a continued dependenceonthe androgen receptor (AR). The proposed mechanisms that underlieAR function in this clinical setting are quite varied. These include intratumoral synthesis of androgens from inactive precursors, increased AR expression, AR activation through tyrosine kinase-dependent signaling, alterations in steroid receptor coactivators, and expression of a truncated AR with constitutive activity. Various pharmacologic interventions have clinically validated some of these mechanisms, such as those that require the AR ligand-binding domain. Clinical studies have failed to validate other mechanisms, and additional mechanisms have yet to be tested in patients with CRPC. Here, we review the mechanisms that elicit AR activity in CRPC, with a particular focus on recent developments.
AB - Systemic treatment of advanced prostate cancer is initiated with androgen deprivation therapy by gonadal testosterone depletion. Response durations are variable and tumors nearly always become resistant as castration-resistant prostate cancer (CRPC), which is driven, at least in part, by a continued dependenceonthe androgen receptor (AR). The proposed mechanisms that underlieAR function in this clinical setting are quite varied. These include intratumoral synthesis of androgens from inactive precursors, increased AR expression, AR activation through tyrosine kinase-dependent signaling, alterations in steroid receptor coactivators, and expression of a truncated AR with constitutive activity. Various pharmacologic interventions have clinically validated some of these mechanisms, such as those that require the AR ligand-binding domain. Clinical studies have failed to validate other mechanisms, and additional mechanisms have yet to be tested in patients with CRPC. Here, we review the mechanisms that elicit AR activity in CRPC, with a particular focus on recent developments.
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U2 - 10.1210/en.2013-1466
DO - 10.1210/en.2013-1466
M3 - Review article
C2 - 24002034
AN - SCOPUS:84886534301
SN - 0013-7227
VL - 154
SP - 4010
EP - 4017
JO - Endocrinology
JF - Endocrinology
IS - 11
ER -