Novel, potent anti-androgens of therapeutic potential: recent advances and promising developments.

Abstract

The beneficial effect of androgen ablation has been well established in prostate cancer therapy. Despite the initial response, patients typically relapse with a more aggressive form described as castration-resistant prostate cancer (CRCP), driven by continued androgen receptor (AR) signaling. This review details the current state of anti-androgen therapy, mainly for CRPC, with major emphasis on the most potent and promising compounds under development. Anti-androgen failure has been linked to elevated AR expression, increased expression of coactivator proteins, AR mutations, ligand-independent AR activation and persistent intraprostatic androgens. MDV3100, BMS-641988 and VN/124-1 were developed to overcome these mechanisms. In CRCP, prostate cancer cells still rely on intracellular androgens and, to a greater extent, on active AR for growth and survival. Therefore, potent anti-androgens that efficiently disrupt the functions (signaling) of AR are envisioned to be effective drugs for all types of prostate cancers.

• Authors: Tadas S Vasaitis, Vincent C O Njar
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 2 Issue 4 Pg. 667-80 (Apr 2010) ISSN: 1756-8927 [Electronic] England
• PMID: 21426013 (Publication Type: Journal Article, Review)

Chemical References

• AR protein, human
• Androgen Antagonists
• Receptors, Androgen

Topics

• Androgen Antagonists (chemical synthesis, chemistry, therapeutic use)
• Humans
• Male
• Molecular Structure
• Prostatic Neoplasms (drug therapy)
• Receptors, Androgen (genetics, metabolism)
• Signal Transduction (physiology)