Adaptation and clonal selection models of castration-resistant prostate cancer: Current perspective

Division of Urology, Department of Surgery, Ahmadu Bello University, Zaria, Nigeria.
International Journal of Urology (Impact Factor: 2.41). 11/2012; 20(4). DOI: 10.1111/iju.12005
Source: PubMed


Prostate cancer is a leading cause of cancer deaths in men worldwide. Management of the disease has remained a great challenge and even more so is the aggressive advanced stage with castration-resistant behavior. The mechanisms and timing of development of castration-resistant prostate cancer are unclear and remain debatable. Progression to castration-resistant prostate cancer is undoubtedly multifactorial, with a number of molecular-genetic aberrations implicated. However, a key question that remains unanswered is: when in the evolution of prostate cancer do the changes that confer castration resistance occur? Earlier attempts to address this question led to two proposed models: the "adaptation" and the "clonal selection" models. Although the prevailing hypothesis is the adaptation model, there is recent evidence in favor of the clonal selection model. Clarification of the model development of castration-resistant prostate cancer might significantly alter our diagnostic and therapeutic strategies, and potentially lead to improved outcome of management of this daunting condition. Here we review existing knowledge and current research findings addressing the timing of events in the course of prostate cancer progression to castration-resistant prostate cancer.

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    • "The mechanism of such benefit is currently unclear. Castrate-resistant clones may be present in the prostate prior to the initiation of ADT and they could be enriched through clonal selection after testosterone decline (Figure 3) (43). Animal models support the use of early local treatment to eliminate androgen-independent clones (44, 45). "
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    • "Most prostate cancers regress after androgen-deprivation or anti-androgen therapy, but the cancers eventually progress into castration-resistant prostate cancer (CRPC) [1]. Because no effective therapeutic regimens are available for CRPC, the recurrence of prostate cancer remains a major challenge for improving clinical outcome [2]. Therefore, it is needed to develop new therapeutic approach for prostate cancer. "
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