Rictor-A Mediator of Progression and Metastasis in Lung Cancer

Simple Summary Despite recent advances in targeted therapy and immunotherapy, the treatment of lung cancer remains challenging due to its high metastatic potential, which adversely affects both the prognosis and the quality of life of these patients. Rictor, the scaffold protein of the mTORC2 complex, plays an important role in regulating essential cellular functions and promoting metastases through epithelial-mesenchymal transition. Amplification of the RICTOR gene and subsequent overexpression of the Rictor protein can activate mTORC2 and promote cell survival and migration. Recent studies suggest that RICTOR amplification and Rictor overexpression may serve as markers of mTORC2 activation. Potentially, they can also provide druggable targets for advanced therapy. Although these drugs are still in a preclinical phase, selective mTORC2 inhibitors are a promising approach to inhibit tumor cell migration and metastasis formation. This review highlights the importance of Rictor and mTORC2 as predictive markers and promising therapeutic targets in the treatment of lung cancer.Abstract 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 RICTOR 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 RICTOR 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, RICTOR 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, RICTOR amplification, mTORC2, Rictor complexes, lung cancer, metastasis, progression, mTOR inhibitors.