Journal
CANCER LETTERS
Volume 367, Issue 1, Pages 12-17Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.06.021
Keywords
Androgen deprivation therapy; Prostate cancer; Castration resistance; Molecular alterations
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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. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
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