Das Plabon Kumar, Islam Farhadul, Smith Robert A, Lam Alfred K
Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.
Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia.
Front Oncol. 2021 Feb 16;10:598957. doi: 10.3389/fonc.2020.598957. eCollection 2020.
Cancer stem cells (CSCs) in esophageal cancer have a key role in tumor initiation, progression and therapy resistance. Novel therapeutic strategies to target CSCs are being tested, however, more in-depth research is necessary. Eradication of CSCs can result in successful therapeutic approaches against esophageal cancer. Recent evidence suggests that targeting signaling pathways, miRNA expression profiles and other properties of CSCs are important strategies for cancer therapy. Wnt/β-catenin, Notch, Hedgehog, Hippo and other pathways play crucial roles in proliferation, differentiation, and self-renewal of stem cells as well as of CSCs. All of these pathways have been implicated in the regulation of esophageal CSCs and are potential therapeutic targets. Interference with these pathways or their components using small molecules could have therapeutic benefits. Similarly, miRNAs are able to regulate gene expression in esophageal CSCs, so targeting self-renewal pathways with miRNA could be utilized to as a potential therapeutic option. Moreover, hypoxia plays critical roles in esophageal cancer metabolism, stem cell proliferation, maintaining aggressiveness and in regulating the metastatic potential of cancer cells, therefore, targeting hypoxia factors could also provide effective therapeutic modalities against esophageal CSCs. To conclude, additional study of CSCs in esophageal carcinoma could open promising therapeutic options in esophageal carcinomas by targeting hyper-activated signaling pathways, manipulating miRNA expression and hypoxia mechanisms in esophageal CSCs.
食管癌中的癌症干细胞（CSCs）在肿瘤起始、进展和治疗抵抗中起关键作用。针对CSCs的新型治疗策略正在进行测试，然而，仍需要更深入的研究。根除CSCs可带来针对食管癌的成功治疗方法。最近的证据表明，靶向CSCs的信号通路、miRNA表达谱和其他特性是癌症治疗的重要策略。Wnt/β-连环蛋白、Notch、Hedgehog、Hippo等通路在干细胞以及CSCs的增殖、分化和自我更新中起关键作用。所有这些通路都与食管CSCs的调控有关，并且是潜在的治疗靶点。使用小分子干扰这些通路或其组成部分可能具有治疗益处。同样，miRNAs能够调节食管CSCs中的基因表达，因此用miRNA靶向自我更新通路可作为一种潜在的治疗选择。此外，缺氧在食管癌代谢、干细胞增殖、维持侵袭性以及调节癌细胞的转移潜能中起关键作用，因此，靶向缺氧因子也可为针对食管CSCs提供有效的治疗方式。总之，对食管癌中CSCs的进一步研究可能通过靶向食管CSCs中过度激活的信号通路、操纵miRNA表达和缺氧机制，为食管癌开辟有前景的治疗选择。
