Szalai Fatime, Sztankovics Dániel, Krencz Ildikó, Moldvai Dorottya, Pápay Judit, Sebestyén Anna, Khoor Andras
Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary.
Department of Laboratory Medicine and Pathology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Cancers (Basel). 2024 Jan 26;16(3):543. doi: 10.3390/cancers16030543.
Lung carcinoma is one of the most common cancer types for both men and women. Despite recent breakthroughs in targeted therapy and immunotherapy, it is characterized by a high metastatic rate, which can significantly affect quality of life and prognosis. Rictor (encoded by the gene) is known as a scaffold protein for the multiprotein complex mTORC2. Among its diverse roles in regulating essential cellular functions, mTORC2 also facilitates epithelial-mesenchymal transition and metastasis formation. Amplification of the gene and subsequent overexpression of the Rictor protein can result in the activation of mTORC2, which promotes cell survival and migration. Based on recent studies, amplification or Rictor overexpression can serve as a marker for mTORC2 activation, which in turn provides a promising druggable target. Although selective inhibitors of Rictor and the Rictor-mTOR association are only in a preclinical phase, they seem to be potent novel approaches to reduce tumor cell migration and metastasis formation. Here, we summarize recent advances that support an important role for Rictor and mTORC2 as potential therapeutic targets in the treatment of lung cancer. This is a traditional (narrative) review based on Pubmed and Google Scholar searches for the following keywords: Rictor, amplification, mTORC2, Rictor complexes, lung cancer, metastasis, progression, mTOR inhibitors.
肺癌是男性和女性中最常见的癌症类型之一。尽管近期在靶向治疗和免疫治疗方面取得了突破，但它的特点是转移率高，这会显著影响生活质量和预后。Rictor（由该基因编码）是多蛋白复合物mTORC2的支架蛋白。在其调节基本细胞功能的多种作用中，mTORC2还促进上皮-间质转化和转移形成。该基因的扩增及随后Rictor蛋白的过表达可导致mTORC2的激活，从而促进细胞存活和迁移。基于最近的研究，该基因扩增或Rictor过表达可作为mTORC2激活的标志物，这反过来提供了一个有前景的可成药靶点。尽管Rictor及Rictor与mTOR关联的选择性抑制剂仅处于临床前阶段，但它们似乎是减少肿瘤细胞迁移和转移形成的有效新方法。在此，我们总结了支持Rictor和mTORC2作为肺癌治疗潜在治疗靶点的重要作用的最新进展。这是一篇基于在PubMed和谷歌学术上搜索以下关键词的传统（叙述性）综述：Rictor、该基因扩增、mTORC2、Rictor复合物、肺癌、转移、进展、mTOR抑制剂。
