Pharmaceutical Research

, Volume 28, Issue 3, pp 423–437 | Cite as

Cholesterol as a Potential Target for Castration-Resistant Prostate Cancer

  • Alexis L. Twiddy
  • Carlos G. Leon
  • Kishor M. WasanEmail author
Expert Review


Advanced prostate cancer (CaP) is often treated with androgen deprivation therapy (ADT). Despite high initial success rates of this therapy, recurrence of the cancer in a castration-resistant (CRPC) form is inevitable. It has been demonstrated that, despite the low levels of circulating androgens resulting from ADT, intratumoral androgen levels remain high and androgen receptor activation persists. Recently, it was discovered that de novo androgen synthesis is occurring within the tumor cells themselves, thus providing a potential mechanism for the high endogenous concentrations. A common upstream precursor in this steroidogenic pathway is cholesterol. For many decades, the breakdown of cholesterol homeostasis in cancer has been the focus of research, but this was largely to elucidate its involvement in maintaining membrane integrity and cell signaling. De novo steroidogenesis has provided a new avenue for cholesterol research and reinforces the importance of understanding the mechanisms that lead to the alterations in cholesterol regulation in the progression to CRPC. The findings to date suggest that cholesterol homeostasis is altered to support de novo androgen synthesis and appear to facilitate disease progression. We further propose that a better understanding of the link between cholesterol and de novo androgen synthesis in CaP progression may provide opportunities for novel therapeutic intervention, namely via eliminating sources of the precursor cholesterol. This review summarizes the implications of cholesterol dysregulation in CaP and particularly in the post-ADT castration-resistant state, as well as the potential implementation of novel therapies targeting these cholesterol sources.


castration resistant prostate cancer cholesterol novel therapeutics targets statins scavenger receptor class B type I 



ATP-binding cassette transporter-subfamily A1


acyl-coenzyme A:cholesterol acyltransferase


androgen deprivation therapy


aldo-keto reductase family 1 members C1/2/3


androgen Receptor


castration-resistant cell line derived from LNCaP


prostate cancer


cholesteryl ester


castration-resistant Prostate Cancer




castration-resistant prostate cancer carcinoma cell line derived from brain metastases


high-density lipoprotein


3-hydroxy-3-methylglutaryl-Coenzyme A reductase


17β-Hydroxy steroid dehydrogenase 3


hormone-sensitive lipase


low-density lipoprotein


lymph node metastatic prostate adenocarcinoma cell line


bone-derived castration-resistant cell line


scavenger Receptor Class B Type I


steroid 5α-reductase Type 1


steroidogenic acute regulatory protein


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Alexis L. Twiddy
    • 1
  • Carlos G. Leon
    • 1
  • Kishor M. Wasan
    • 1
    Email author
  1. 1.Division of Pharmaceutics and Biopharmaceutics Faculty of Pharmaceutical SciencesThe University of British ColumbiaVancouverCanada

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