Current and potential targets for drug design in the androgen receptor pathway for prostate cancer

ABSTRACT

Introduction: Modulating the androgen axis by different agents has been one of the most successful therapeutic interventions in the field of prostate cancer therapy. Newer agents such as abiraterone and enzalutamide have been widely adapted and have contributed to an increase in the overall survival of prostate cancer patients. However, most of these patients will develop resistance to these agents and will need chemotherapy.

Areas covered: In this review, this author discusses current agents which modulate the androgen axis, the mechanisms of resistance to these agents and investigative agents which are designed to bypass these mechanisms of resistance. Potential targets in the androgen axis and related biochemical pathways are, furthermore, identified.

Expert opinion: Understanding the mechanism of resistance to these agents is crucial in developing third generation anti-androgen agents which can potentially contribute to the longevity of prostate cancer patients to a greater extent. Besides developing more potent agents, it is also important to formulate new strategies to resensitize patients to current anti-androgen agents by carefully sequencing chemotherapy regimens and abrogating genetic changes which are known to cause resistance to anti-androgens. Combinatorial approach with immunotherapy offers prospects which may yield better results and need to be thoroughly explored.

KEYWORDS:

• Androgen
• Prostate cancer
• therapy

Article highlights

• Modulation of the androgen axis is an important part of management of prostate cancer.

• Resistance to current agents can be divided into androgen receptor dependent and independent mechanisms.

• Several mutations in the androgen receptor have been identified and have been correlated with development of resistance to current agents.

• Newer agents are being designed to different parts of the androgen receptors to help overcome the resistance due to these mutations.

There are several targets in the androgen receptor pathway that may have therapeutic value.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript has not been funded.