Cancer stem cells in prostate cancer radioresistance.

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 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 letters. 2019 Sep 04 [Epub ahead of print]

Tsao Tsing, Julia Beretov, Jie Ni, Xupeng Bai, Joseph Bucci, Peter Graham, Yong Li

St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, 2052, Australia; Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia., St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, 2052, Australia; Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia; Anatomical Pathology, NSW Health Pathology, St. George Hospital, Kogarah, NSW, 2217, Australia., St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, 2052, Australia; Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia; School of Basic Medical Sciences, Zhengzhou University, Henan, 450001, China. Electronic address: .