环状 RNA 在食管鳞癌的临床前和模型中具有疗效。
Circular RNAs With Efficacy in Preclinical and Models of Esophageal Squamous Cell Carcinoma.
机构信息
Roche Pharma Research and Early Development (pRED), Large Molecule Research, Roche Innovation Center Munich, Penzberg, Germany
Roche Pharma Research and Early Development (pRED), Large Molecule Research, Roche Innovation Center Munich, Penzberg, Germany.
出版信息
Cancer Genomics Proteomics. 2022 May-Jun;19(3):283-298. doi: 10.21873/cgp.20320.
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.
食管癌预后不良。已批准的药物武器集中在化疗上，治疗效果有限。最近，检查点抑制单克隆抗体 Pembrolizumab 获得批准。为了寻找治疗食管鳞癌（ESCC）的新靶点和方法，我们在文献中搜索了与 ESCC 发病机制相关的 circRNAs。我们发现了两个下调和 17 个上调的 circRNAs，以及一种在临床前体内系统中有效的合成 circRNA。下调的 circRNAs 可吸收针对肿瘤抑制基因的 microRNAs。上调的 circRNAs 可吸收针对编码具有促肿瘤功能的蛋白质的 mRNAs 的 microRNAs。我们讨论了一些问题，如下调的 circRNAs 的重建和用短干扰 RNA（siRNA）相关物质抑制上调的 circRNAs。此外，我们还讨论了所鉴定的靶标的成药性问题。
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