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.
Cancer Genomics Proteomics. 2023 May-Jun;20(3):222-238. doi: 10.21873/cgp.20377.
In order to identify new targets and treatment modalities for breast cancer, we searched the literature for circular RNAs (circRNAs) with efficacy in preclinical breast cancer-related in vivo models. From our search, we identified 26 up-regulated and six down-regulated circRNAs which mediate efficacy in breast cancer-related preclinical in vivo models. We discuss reconstitution and inhibition of the identified circRNAs, as well as druggability and validation of the targets identified in the context of chemoresistance, inhibition of proliferation and metastasis. Pathways driven by suppressors of cytokines and high-mobility group proteins, nuclear factor B and Hippo signaling emerged as important drivers of tumor growth and metastasis. The role of trefoil factor-1 with respect to metastasis of estrogen receptor-positive breast cancer also merits further investigation. In addition, mucin 19 has emerged as an unexplored target for treatment of breast cancer.
为了确定乳腺癌的新靶点和治疗方法,我们在文献中搜索了在临床前乳腺癌相关动物模型中具有疗效的环状 RNA(circRNA)。在我们的研究中,发现了 26 个上调和 6 个下调的 circRNA,它们在乳腺癌相关的临床前动物模型中具有疗效。我们讨论了鉴定出的 circRNA 的重建和抑制,以及药物靶标在化疗耐药、增殖和转移抑制方面的验证。细胞因子和高迁移率族蛋白、核因子 B 和 Hippo 信号通路的抑制剂所驱动的通路被认为是肿瘤生长和转移的重要驱动因素。三叶因子 1 与雌激素受体阳性乳腺癌转移的关系也值得进一步研究。此外,粘蛋白 19 已成为治疗乳腺癌的一个未经探索的靶点。