The promise of mTOR inhibitors in the treatment of colorectal cancer.

INTRODUCTION: Recently, deregulation of protein synthesis has begun to gain attention as a major player in cancer development and progression. Specifically, deregulation of the process of translation initiation appears to play a key role in oncogenesis. The PI3K/Akt/mTOR pathway is vital for cellular metabolism, growth and proliferation and thus an attractive therapeutic target in oncology. Accordingly, several mTOR inhibitors are currently being tested in many cancers including colorectal cancer (CRC). AREAS COVERED: In this review, the key components of the PI3K/Akt/mTOR pathways, their molecular alterations and the inhibitors targeting the mTOR pathway in CRC are described. Complex interactions with other pathways such as the MAPK pathway are analyzed, as are possible drug combinations that target this pathway. In addition, novel strategies for use of mTOR pathway inhibitors in CRC treatment are introduced. EXPERT OPINION: Clinical trials of mTOR inhibitors have been investigated in CRC. mTOR inhibitors may represent an attractive antitumor target in combination with strategies to target other pathways that may overcome resistance. Further research is needed to identify critical molecular effector mechanisms, molecular markers that predict responsiveness and potential toxicities.