The phosphoinositide 3-kinase pathway and cancer
Human tumours emerge as the result of multiple genetic and epigenetic aberrations that allow the proto-cancer cell to escape normal social control. Many signal transduction pathways become constitutively active during this process, and one whose importance is increasingly being appreciated involves phosphoinositide 3-kinase (PI3-kinase). This pathway normally regulates important cell decisions such as growth, division, survival and migration, and when deregulated it can confer malignant potential to the ensuing tumour. However, constitutive activation of the PI3-kinase pathway might provide attractive therapeutic targets for the design of small-molecule inhibitors. This review discusses events upstream and downstream of PI3-kinase activity in the PI3-kinase signalling pathway, how PI3-kinase is deregulated in human tumourigenesis, and how this is being targeted clinically.
Key Words: PI3-kinase; PKB/Akt; mTOR; cancer; therapy.
c1 UCSF Cancer Research Institute, 2340 Sutter Street, Room N319, San Francisco, CA 94115, USA. Tel: +1 415 502 2598; Fax: +1 415 502 3179; E-mail: [email protected]