Emergence of metastatic hormone-refractory disease in prostate cancer after anti-androgen therapy.
The anti-androgens used in prostate cancer therapy have been designed to interfere with the normal androgen receptor (AR)-mediated processes that ensure prostate cell survival, triggering tumor cells to undergo programmed cell death. While anti-androgens were originally designed to treat advanced disease, they have recently been used to debulk organ-confined prostate tumors, to improve positive margins prior to surgery, and for chemoprevention in patients at high risk for prostate cancer. However, tumors treated with anti-androgens frequently become hormone refractory and acquire a more aggressive phenotype. Progression toward metastatic hormone-refractory disease has often been regarded as the outgrowth of a small number of hormone-independent cells that emerge from a hormone-dependent tumor during anti-androgen treatment by natural selection. While a number of selective advantages have recently been identified, there is also considerable evidence suggesting that the progression toward metastatic hormone-refractory disease is an dynamic process which involves abrogation of programmed cell death as a result of the attenuation of DNA fragmentation and maintenance of mitochondrial membrane potential in tumor cells; the upregulation of stromal-mediated growth factor signaling pathways; and the upregulation of extracellular matrix (ECM) protease expression.
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Edmund Chun Yu
EC
Lee
Martin P R
MP
Tenniswood
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology
D000726:Androgen Antagonists; D000728:Androgens