Unit of Experimental Oncology, Clinical and Experimental Medicine Department, University of Parma, Via Volturno 39, 43126 Parma, Italy.
Biochem Pharmacol. 2014 Aug 1;90(3):197-207. doi: 10.1016/j.bcp.2014.05.011. Epub 2014 May 24.
While PI3K/AKT/mTOR pathway is altered in a variety of cancers including non small cell lung cancer, abnormalities in this pathway are more common in squamous cell lung carcinoma than in adenocarcinoma of the lung. Moreover, aberrant activation of PI3K/AKT/mTOR pathway is one of the mechanisms of acquired resistance to EGFR-TK inhibitors in patients with adenocarcinoma carrying EGFR activating mutations. Several inhibitors of the PI3K pathway are undergoing evaluation in preclinical and clinical studies. These include pan and selective inhibitors of PI3K, AKT inhibitors, rapamycin and rapalogs for mTOR inhibition, dual mTORC1-mTORC2 inhibitors and dual PI3K-mTOR inhibitors. This review focuses on recent preclinical and clinical data on the efficacy of PI3K pathway inhibitors in NSCLC either as monotherapy approach or in combination with chemotherapy or with drugs that target other signaling transduction pathways.
尽管 PI3K/AKT/mTOR 通路在多种癌症中发生改变，包括非小细胞肺癌，但在肺鳞癌中，该通路的异常比肺腺癌更为常见。此外，PI3K/AKT/mTOR 通路的异常激活是携带 EGFR 激活突变的腺癌患者对 EGFR-TKI 获得性耐药的机制之一。目前正在进行临床前和临床研究，以评估多种 PI3K 通路抑制剂。这些抑制剂包括 PI3K 的泛和选择性抑制剂、AKT 抑制剂、雷帕霉素和 mTOR 抑制的 rapalog、双重 mTORC1-mTORC2 抑制剂和双重 PI3K-mTOR 抑制剂。本文重点介绍了 PI3K 通路抑制剂在 NSCLC 中作为单药治疗或联合化疗或靶向其他信号转导通路药物的最新临床前和临床数据。
