Roche Pharma Research and Development, Roche Innovation Center, Penzberg, Germany;
Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland
Cancer Genomics Proteomics. 2023 Mar-Apr;20(2):117-131. doi: 10.21873/cgp.20368.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with insufficient options for therapy. In order to identify new targets and treatment modalities we searched the literature for circular RNAs (circRNAs) which mediate efficacy in TNBC-related in vivo preclinical models. In addition to 5 down-regulated circRNAs which modulate tumor-suppressive pathways, we identified 15 up-regulated circRNAs. Down- and up-regulated refers to expression in corresponding non-transformed cells and tissues. The up-regulated circRNAs comprise five transmembrane receptors and secreted proteins as targets, five transcription factors and transcription-associated targets, four cell-cycle related circRNAs and one involved in paclitaxel resistance. In this review article we discuss drug-discovery related aspects and modalities of therapeutic intervention. Down-regulated circRNAs can be reconstituted by re-expression of corresponding circRNAs in tumor cells or up-regulation of corresponding targets. Up-regulated circRNAs can be inhibited by small-interfering RNA (siRNA) or short hairpin RNA (shRNA)-based approaches or inhibition of the corresponding targets with small molecules or antibody-related moieties.
三阴性乳腺癌（TNBC）是一种侵袭性的乳腺癌亚型，治疗选择有限。为了寻找新的治疗靶点和方法，我们在文献中搜索了circRNAs（环状 RNA），这些circRNAs 在与 TNBC 相关的体内临床前模型中具有疗效。除了 5 个下调的circRNAs 调节肿瘤抑制途径外，我们还鉴定了 15 个上调的circRNAs。下调和上调是指在相应的非转化细胞和组织中的表达。上调的 circRNAs 包括五个跨膜受体和分泌蛋白作为靶点，五个转录因子和转录相关靶点，四个细胞周期相关的 circRNAs 和一个与紫杉醇耐药相关的 circRNA。在这篇综述文章中，我们讨论了与药物发现相关的方面和治疗干预的模式。下调的 circRNAs 可以通过在肿瘤细胞中重新表达相应的 circRNAs 或上调相应的靶点来重建。上调的 circRNAs 可以通过 siRNA 或 shRNA 方法抑制，或通过小分子或抗体相关部分抑制相应的靶点。
