Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer.
Clinical data and models of human disease indicate that androgen receptor (AR) activity is essential for prostate cancer development, growth, and progression. The dependence of prostatic adenocarcinoma on AR signaling at all stages of disease has thereby been exploited in the treatment of disseminated tumors, for which ablation of AR function is the goal of first-line therapy. Although these strategies are initially effective, recurrent tumors arise with restored AR activity, and no durable treatment has yet been identified to combat this stage of disease. New insights into AR regulation and the mechanisms underlying resurgent AR activity have provided fertile ground for the development of novel strategies to more effectively inhibit receptor activity and prolong the transition to therapeutic failure.
Knudsen
Karen E
KE
Departments of Cancer Biology, Urology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. karen.knudsen@kimmelcancercenter.org
Scher
Howard I
HI
D000726:Androgen Antagonists / Q000627:therapeutic use; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000378:metabolism; D000813:Anilides / Q000627:therapeutic use; D005485:Flutamide / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009570:Nitriles / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014105:Tosyl Compounds / Q000627:therapeutic use
C410798:AR protein, human; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D005485:Flutamide; C053541:bicalutamide