Sun Shi-Yong
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Chin J Cancer. 2013 May;32(5):270-4. doi: 10.5732/cjc.013.10005. Epub 2013 Mar 15.
Rapamycin and its derivatives (rapalogs), a group of allosteric inhibitors of mammalian target of rapamycin (mTOR), have been actively tested in a variety of cancer clinical trials, and some have been approved by the Food and Drug Administration for the treatment of certain types of cancers. However, the single agent activity of these compounds in many tumor types remains modest. The mTOR axis is regulated by multiple upstream signaling pathways. Because the genes (e.g., PIK3CA, KRAS, PTEN, and LKB1) that encode key components in these signaling pathways are frequently mutated in human cancers, a subset of cancer types may be addicted to a given mutation, leading to hyperactivation of the mTOR axis. Thus, efforts have been made to demonstrate the potential impact of genetic alterations on rapalog-based or mTOR-targeted cancer therapy. This review will primarily summarize research advances in this direction.
雷帕霉素及其衍生物（雷帕霉素类似物）是一组哺乳动物雷帕霉素靶蛋白（mTOR）的变构抑制剂，已在多种癌症临床试验中积极开展测试，其中一些已获美国食品药品监督管理局批准用于治疗某些类型的癌症。然而，这些化合物在许多肿瘤类型中的单药活性仍然有限。mTOR轴由多个上游信号通路调控。由于编码这些信号通路关键组分的基因（如PIK3CA、KRAS、PTEN和LKB1）在人类癌症中经常发生突变，一部分癌症类型可能对特定突变存在依赖，导致mTOR轴过度激活。因此，人们一直在努力证明基因改变对基于雷帕霉素类似物或mTOR靶向的癌症治疗的潜在影响。本综述将主要总结这一方向的研究进展。
