The androgen receptor as a therapeutic target in prostate cancer

Abstract

The most critical problem in the treatment of prostate cancer is the emergence of hormone-refractory tumour during hormonal therapy. Although the vast majority of patients initially have an excellent response to androgen withdrawal, disease will often return later. There is no effective treatment for such hormone-refractory prostate cancer. Despite the fact that the mechanisms leading to transition from androgen-dependent to androgen-independent disease have been extensively studied, they have mostly remained unclear. It was earlier considered that the growth of hormone-refractory tumour is independent of androgens and androgen receptor (AR) signalling pathways. Recently, however, several studies have indicated that aberrations in the AR signalling pathway could actually be key mechanisms in androgen independence. For example, the revelations of AR gene amplification, mutations and cross-talk with the ERBB2 pathway suggest that AR is still operational in hormone-refractory tumours. Thus, AR is a putative new-old target for novel treatment modalities.

• amplification
• androgen receptor
• androgen withdrawal
• castration
• ERBB2
• Her-2/neu
• hormonal therapy
• mutation
• prostate cancer