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Esophageal cancer is associated with a dismal prognosis. The armamentarium of approved drugs is focused on chemotherapy with modest therapeutic benefit. Recently, checkpoint inhibitory monoclonal antibody Pembrolizumab was approved. In order to identify new targets and modalities for the treatment of esophagus squamous cell carcinoma (ESCC) we searched the literature for circRNAs involved in the pathogenesis of ESCC. We identified two down-regulated and 17 up-regulated circRNAs as well as a synthetic circRNA with efficacy in preclinical in vivo systems. Down-regulated circRNAs sponge microRNAs directed against tumor suppressor genes. Up-regulated circRNAs sponge microRNAs directed against mRNAs, which encode proteins with pro-tumoral functions. We discuss issues such as reconstitution of down-regulated circRNAs and inhibition of up-regulated circRNAs with short interfering RNA (siRNA)- related entities. Also, we address druggability issues of the identified targets.

Circular RNAs With Efficacy in PreclinicalIn VitroandIn VivoModels of Esophageal Squamous Cell Carcinoma