Cancer Stem Cells in Prostate Cancer Chemoresistance
Jie Ni, Paul Cozzi, Jingli Hao, Wei Duan, Peter Graham, John Kearsley and Yong Li
Pages 225-240 (16)
There is currently no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and
metastatic disease remain the main causes of treatment failure and mortality in CaP patients. Although several advances
have been made in the control of CRPC with some newly developed drugs, there is still an urgent need to investigate the
mechanisms and pathways of prostate cancer (CaP) metastasis and chemoresistance, identify useful therapeutic targets,
develop novel treatment approaches, improve current therapeutic modalities and increase patients' survival. Cancer stem
cells (CSCs), a minority population of cancer cells characterised by self-renewal and tumor initiation, have gained intense
attention as they not only play a crucial role in cancer recurrence but also contribute substantially to chemoresistance. As
such, a number of mechanisms in chemoresistance have been identified to be associated with CSCs. Therefore, a thorough
and integral understanding of these mechanisms can identify novel biomarkers and develop innovative therapeutic
strategies for CaP treatment. Our recent data have demonstrated CSCs are associated with CaP chemosensitivity. In this
review, we discuss the roles of putative CSC markers in CaP chemoresistance and elucidate several CSC-associated
signaling pathways such as PI3K/Akt/mTOR, Wnt/β-catenin and Notch pathways in the regulation of CaP
chemoresistance. Moreover, we will summarize emerging and innovative approaches for the treatment of CRPC and
address the challenging CRPC that is driven by CSCs. Understanding the link between CSCs and metastatic CRPC will
facilitate the development of novel therapeutic approaches to overcome chemoresistance and improve the clinical
outcomes of CaP patients.
Cancer stem cell, castration-resistant prostate cancer, chemoresistance, EMT, prostate cancer, treatment.
Cancer Care Centre, St George Hospital, Gray St, Kogarah, Sydney, NSW 2217, Australia.