Cancer stem cells in prostate cancer radioresistance

• Published in: Cancer letters Vol. 465; pp. 94 - 104
• Main Authors: Tsao, Tsing, Beretov, Julia, Ni, Jie, Bai, Xupeng, Bucci, Joseph, Graham, Peter, Li, Yong
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28.11.2019; Elsevier Limited
• Subjects: Aldehyde dehydrogenase; Androgens; Angiogenesis; Angiogenesis inhibitors; Anticancer therapy; Apoptosis; Autophagy; Biomarkers, Tumor - metabolism; Cancer stem cells; Cancer therapies; CD44 antigen; Cell division; Chemokines; DNA repair; Epithelial-Mesenchymal Transition; Growth factors; Heterogeneity; Humans; Hypoxia; Inhibitors; Integrins; Kinases; Male; Medical research; Mesenchyme; Metastases; Metastasis; Metformin; Neoplastic Stem Cells - metabolism; Phagocytosis; Prognosis; Prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - radiotherapy; Proteins; Radiation Tolerance; Radioresistance; Radiosensitisation; Reactive oxygen species; Reactive Oxygen Species - metabolism; Stem cells; Transcription factors; Tumor Microenvironment; Tumors; Wnt protein; Radioresistance; Cancer stem cells; Radiosensitisation; Anticancer therapy; Prostate cancer
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2019.08.020

Cancer stem cells (CSCs) in prostate cancer (CaP) are regarded as major contributors to radioresistance due to complex mechanisms including enhanced DNA repair, increased intracellular reactive oxygen species scavenging, activation of anti-apoptotic pathways, microenvironment hypoxia, epithelial-to-mesenchymal transition (EMT) and autophagy. They are also believed to cause tumour recurrence and metastasis due to their unique capability to survive and replicate the heterogeneity of the original tumour. Finding markers of prostate CSCs (PCSC) for identification, prognostication and targeting is key in enhancing therapeutic and clinical outcomes. Markers such as aldehyde dehydrogenase, CD44, integrins and EMT markers have been proved to show great potential in being sensitive and specific to the presence of PCSCs. Novel therapies such as Hedgehog and Wnt pathway inhibitors, angiogenesis inhibitors and metformin show potential in eliminating PCSCs to improve therapeutic outcomes. Here, we review the current state of the literature regarding mechanisms of PCSC radioresistance, promising PCSC markers and novel PCSC-specific therapeutic approaches and their implications in CaP treatment and prognosis. •Cancer stem cells play important roles in prostate cancer radioresistance and recurrence.•Cancer stem cells have great potential as biomarkers for prostate cancer prognosis and therapy.•Novel therapies are emerging to specifically target cancer stem cells in prostate cancer to improve therapeutic outcomes.•Further research into cancer stem cells in prostate cancer could possibly allow the prediction of radioresistance, metastatic and recurrence risk in prostate cancer patients.•Accurate, reliable characterization of cancer stem cells in prostate cancer could also allow personalised therapeutic intervention in radiotherapy.