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Molecular Mechanisms of Castrate Resistant Prostate Cancer

  • Francois Lamoureux
  • Amina Zoubeidi
  • Martin E. Gleave
Chapter

Abstract

Cancer has replaced heart disease as the leading cause of death in North America – nearly half will develop cancer, and one in four will die from the disease [1]. Prostate cancer (PCa) is the most common male cancer in North America and 2nd leading cause of cancer deaths, but even more importantly, its incidence and mortality will double by 2020 based on current incidence trends. PCa represents 1 % of all death and 13 % of death by cancer [2]. While many gains have been made in early detection and treatment of localized PCa, many men still die of recurrent or metastatic disease. Androgen ablation remains the most effective therapy for patients with advanced disease. While ∼80 % of patients initially respond, most patients progress to castrate resistant prostate cancer (CRPC) metastatic disease after 18–36 months [3–15]. Androgen ablation precipitates apoptosis in subpopulations of PCa cells, but despite high initial response rates, remissions are temporary because surviving tumor cells usually recur with a castrate resistant phenotype [15, 16]. CRPC progression is a complex process by which cells acquire the ability to both survive and proliferate in the absence of androgens and involves variable combinations of clonal selection [17], the reactivation of the androgen receptor axis [18], as well as adaptive upregulation of anti-apoptotic genes [19–25], alternative growth factor pathways [26–32], and cytoprotective chaperone networks [22, 33]. Clinically, CRPC is defined as biochemical and/or radiographic progression despite castrate levels of serum testosterone (<50 ng/ml) [34]. Biochemical progression is defined as two consecutive increases in prostate-specific antigen (PSA) above a minimal value of 5 ng/ml. Usually, progression occurs following cessation of treatment with androgen blockers for 4–6 weeks.

Keywords

Epidermal Growth Factor Receptor Androgen Receptor Bone Metastasis LNCaP Cell Abiraterone Acetate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  • Francois Lamoureux
    • 1
  • Amina Zoubeidi
    • 1
  • Martin E. Gleave
    • 1
    • 2
  1. 1.Department of Urologic SciencesVancouver Prostate Centre, Vancouver General HospitalVancouverCanada
  2. 2.Department of Urologic SciencesUniversity of British ColumbiaVancouverCanada

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