Targeting phosphoinositide 3-kinase for cancer therapy


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Lewis C Cantley1
1Weill Cornell Medical School, Cornell University, New York, USA

Abstract

Lay abstract:

Phosphoinositide 3-kinase (PI3K) mediates glucose uptake into muscle and fat and other tissues in response to insulin, IGF1 and other growth factors. Thus, it plays a major role in the growth of all tissues during human development. Sporadic activating mutations in the gene encoding PI3K (PIK3CA) or inactivating mutations in PTEN, a gene that reverses the effects of PI3K, are among the most common events in solid tumours. These mutations allow tumours to take up glucose and use it for tumour growth. More than thirty drugs that target PI3K and other components of this pathway are in clinical trials for a variety of cancers. It is likely that PI3K pathway inhibitors will need to be combined with other drugs to be broadly effective. We have been using pre-clinical models to determine how best to determine what patients are most likely to benefit from treatment with PI3K inhibitors as single agent drugs or in combination with other drugs. The role of PI3K inhibitors for treating cancers in pre-clinical models and in human trials will be discussed.