Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland
Cancer Genomics Proteomics. 2022 Jul-Aug;19(4):372-389. doi: 10.21873/cgp.20327.
Esophageal squamous cell carcinoma is a type of cancer with dismal prognosis. Surgery, chemo- and radiation therapy, as well as immune checkpoint-blocking immunotherapy lead to limited improvement of survival of patients; therapy resistance and recurrencies hamper these treatment modalities. Therefore, the identification of new targets and treatment approaches is of paramount importance. We have searched the literature and identified 7 down-regulated and 16 up-regulated non-coding RNAs, which showed efficacy in preclinical esophageal squamous cell carcinoma-related in vitro and in vivo models, and discuss their diverse mode of actions. We excluded long non-coding RNAs, which act by sponging of microRNAs. It is presently unclear whether long non-coding RNA/protein, DNA and RNA interactions can be targeted with small molecules. We describe reconstitution therapy and inhibition of the corresponding long non-coding RNAs with small interfering RNAs and antisense oligonucleotides. Also, we discuss emerging targets for treatment of esophageal squamous cell carcinoma.
食管鳞状细胞癌是一种预后不良的癌症。手术、化疗、放疗以及免疫检查点阻断免疫疗法仅能有限地改善患者的生存率；治疗耐药和复发阻碍了这些治疗方法的应用。因此，确定新的靶点和治疗方法至关重要。我们查阅了文献，确定了 7 个下调和 16 个上调的非编码 RNA，这些 RNA 在食管鳞状细胞癌相关的体外和体内模型中显示出疗效，并讨论了它们不同的作用模式。我们排除了长链非编码 RNA，其通过海绵作用于 microRNAs。目前尚不清楚是否可以用小分子靶向长链非编码 RNA/蛋白质、DNA 和 RNA 相互作用。我们描述了用小分子、小干扰 RNA 和反义寡核苷酸进行重建治疗和抑制相应的长链非编码 RNA。此外，我们还讨论了治疗食管鳞状细胞癌的新靶点。
