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前列腺癌放射抵抗中的癌症干细胞。

Cancer stem cells in prostate cancer radioresistance.

机构信息

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.

出版信息

Cancer Lett. 2019 Nov 28;465:94-104. doi: 10.1016/j.canlet.2019.08.020. Epub 2019 Sep 4.

Abstract

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.

摘要

前列腺癌中的癌症干细胞(CSC)被认为是导致放射抵抗的主要因素,其复杂的机制包括增强的 DNA 修复、增加的细胞内活性氧物质清除、抗凋亡途径的激活、微环境缺氧、上皮-间充质转化(EMT)和自噬。由于其独特的生存和复制原始肿瘤异质性的能力,它们也被认为会导致肿瘤复发和转移。寻找前列腺 CSC(PCSC)的标志物用于鉴定、预后和靶向治疗是提高治疗效果和临床结果的关键。醛脱氢酶、CD44、整合素和 EMT 标志物等标记物已被证明在敏感和特异性地检测 PCSC 方面具有很大的潜力。新型治疗方法,如 Hedgehog 和 Wnt 通路抑制剂、血管生成抑制剂和二甲双胍,显示出消除 PCSC 以改善治疗效果的潜力。在这里,我们回顾了有关 PCSC 放射抵抗机制、有前途的 PCSC 标志物和新型 PCSC 特异性治疗方法的文献现状,以及它们在前列腺癌治疗和预后中的意义。

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