Molecular processes leading to aberrant androgen receptor signaling and castration resistance in prostate cancer

Abstract

Hormone therapies targeting androgen receptor signaling are the mainstay of treatment for patients with advanced prostate cancer. The length of clinical remission induced by hormone therapies varies substantially among treated patients. Why some patients progress rapidly after treatment while others benefit with prolonged remission is a question that remains unsolved. The androgen receptor signaling pathway is the key molecular determinant of castration resistance, and a key target for prostate cancer drug design. Recent advances in characterizing molecular processes leading to the development of castration-resistant prostate cancer, including the discovery of multiple androgen receptor splicing variants, offer opportunities for rational development of new clinical tools or approaches to predict, monitor or control/prevent prostate cancer progression in the castrate setting.

Keywords::

• androgen receptor
• AR
• AR signaling
• AR splicing variants
• castration-resistant prostate cancer
• CRPC
• hormone therapy
• prostate cancer

Financial & competing interests disclosure

Jun Luo received funding from the David H Koch Foundation, and the Patrick C Walsh Prostate Cancer Research Fund for his research on advanced prostate cancer. The Johns Hopkins University has filed an international patent for using androgen receptor variants as biomarkers and therapeutic targets for advanced prostate cancer. Rong Hu and Jun Luo are co-inventors of this pending patent. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.