Impact of genetic alterations on mTOR-targeted cancer therapy

• Type of Material: Article
• Authors: Shi-Yong Sun, Emory University
• Language: English
• Date: 2013-05
• Publisher: Sun Yat-sen University Cancer Center
• Publication Version: Final Published Version
• Copyright Statement: © Chinese Journal of Cancer
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://www.cjcsysu.cn/abstract.asp?fr=doi&idno=20504
• Title of Journal or Parent Work: Chinese Journal of Cancer
• ISSN: 1000-467X
• Volume: 32
• Issue: 5
• Start Page: 270
• End Page: 274
• Grant/Funding Information: This study was supported by grants from the Georgia Cancer Coalition Distinguished Cancer Scholar award and NIH R01 CA118450, R01 CA160522 and P01 CA116676.
• Keywords: Mutation; rapalogs; cancer; mTOR
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

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.