Zhu Qingyun, Shen Yingying, Chen Xiguang, He Jun, Liu Jianghua, Zu Xuyu
Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, People's Republic of China.
Department of Spine Surgery, The Affiliated Nanhua Hospital of University of South China, Hengyang, Hunan 421001, People's Republic of China.
Onco Targets Ther. 2020 Jan 16;13:525-540. doi: 10.2147/OTT.S224465. eCollection 2020.
The poor survival and prognosis of individuals with cancer are often attributed to tumour relapse and metastasis, which may be due to the presence of cancer stem cells (CSCs). CSCs have the characteristics of self-renewal, differentiation potential, high carcinogenicity, and drug resistance. In addition, CSCs exhibit many characteristics similar to those of embryonic or tissue stem cells while displaying persistent abnormal activation of self-renewal pathways associated with development and tissue homeostasis, including the Wnt, Notch, Hedgehog (Hh), TGF-β, JAK/STAT3, and NF-κB pathways. Therefore, we can eliminate CSCs by targeting these self-renewal pathways to constrain stem cell replication, survival and differentiation. At the same time, we cannot neglect the ping-pong effect of the tumour microenvironment, which releases cytokines and promotes self-renewal pathways in CSCs. Recently, meaningful progress has been made in the study of inhibitors of self-renewal pathways in tumours. This review primarily summarizes several representative and novel agents targeting these self-renewal signalling pathways and the tumour microenvironment and that represent a promising strategy for treating refractory and recurrent cancer.
癌症患者较差的生存率和预后通常归因于肿瘤复发和转移，这可能是由于癌症干细胞（CSCs）的存在。癌症干细胞具有自我更新、分化潜能、高致癌性和耐药性等特征。此外，癌症干细胞表现出许多与胚胎干细胞或组织干细胞相似的特征，同时显示出与发育和组织稳态相关的自我更新途径的持续异常激活，包括Wnt、Notch、Hedgehog（Hh）、TGF-β、JAK/STAT3和NF-κB途径。因此，我们可以通过靶向这些自我更新途径来消除癌症干细胞，以限制干细胞的复制、存活和分化。同时，我们不能忽视肿瘤微环境的乒乓效应，它会释放细胞因子并促进癌症干细胞中的自我更新途径。最近，在肿瘤自我更新途径抑制剂的研究方面取得了有意义的进展。这篇综述主要总结了几种针对这些自我更新信号通路和肿瘤微环境的代表性新型药物，它们代表了一种治疗难治性和复发性癌症的有前景的策略。
