title: Androgen deprivation of prostate cancer: Leading to a therapeutic dead end.
abstract: Androgen deprivation therapy (ADT) is considered as the standard therapy for men with de novo or recurrent metastatic prostate cancer. ADT commonly leads to initial biochemical and clinical responses. However, several months after the beginning of treatment, tumors become castration-resistant and virtually all patients show disease progression. At this stage, tumors are no longer curable and cancer treatment options are only palliative. In this review, we describe molecular alterations in tumor cells during ADT, which lead to deregulation of different signaling pathways and castration-resistance, and how they might interfere with the clinical outcome of different second-line therapeutics. A recent breakthrough finding that early chemotherapy is associated with a significant survival benefit in metastatic hormone-sensitive disease highlights the fact that there is time for a fundamental paradigm shift in the treatment of advanced prostate cancer. Therapeutic intervention seems to be indicated before a castration-resistant stage is reached to improve therapeutic outcome and to reduce undesirable side effects.
authors.affiliation: Department of Urology, Medical Center, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Katzenwadel
authors.affiliation: Department of Urology, Medical Center, University of Freiburg, Engesser Strasse 4b, D-79108 Freiburg, Germany. Electronic address: philipp.wolf@uniklinik-freiburg.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wolf
mesh_terms: D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal
keywords: Androgen deprivation therapy; Castration resistance; Molecular alterations; Prostate cancer