PI3 kinase inhibitors in the clinic: an update.

The phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been identified as a key signaling pathway for important cellular functions such as growth control, metabolism and translation initiation. Several proteins within this pathway are valuable anticancer drug targets, among which several inhibitors of mTOR are now administered in routine practice. A better understanding of the structure and functions of PI3K has led to the development of novel inhibitors that have a more favorable toxicity profile as compared to the first generation of anti-PI3K drugs. In this article, we review the basics of PI3K biology and focus on its inhibitors, currently under investigation in clinical trials. The perspective for future directions in the setting of PI3K inhibition and novel trials is also discussed.