The androgen receptor in hormone-refractory prostate cancer.
Advanced prostate cancer is responsive to hormone therapy that interferes with androgen receptor (AR) signalling. However, the effect is short-lived, as nearly all tumours progress to a hormone-refractory (HR) state, a lethal stage of the disease. Intuitively, the AR should not be involved because hormone therapy that blocks or reduces AR activity is not effective in treating HR tumours. However, there is still a consensus that AR plays an essential role in HR prostate cancer (HRPC) because AR signalling is still functional in HR tumours. AR signalling can be activated in HR tumours through several mechanisms. First, activation of intracellular signal transduction pathways can sensitize the AR to castrate levels of androgens. Also, mutations in the AR can change AR ligand specificity, thereby allowing it to be activated by non-steroids or anti-androgens. Finally, overexpression of the wild-type AR sensitizes itself to low concentrations of androgens. Therefore, drugs targeting AR signalling could still be effective in treating HRPC.
Mao
Hai-Lei
HL
State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Zhu
Zhi-Qi
ZQ
Chen
Charlie Degui
CD
D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000502:physiology; D006801:Humans; D008024:Ligands; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D000726:Androgen Antagonists; D000728:Androgens; D008024:Ligands; D011944:Receptors, Androgen