Therapeutic Strategies Against Cancer Stem Cells in Esophageal Carcinomas.

Abstract

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.