Introduction: Phosphoinositol signalling and cancer


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Bart Vanhaesebroeck1
1Barts Cancer Centre, London, UK

Abstract

Phosphoinositide (PI) lipid metabolism is often deregulated in cancer, and several of the enzymes that underlie this deregulation are emerging targets for therapeutic intervention.

PIs in membranes have both structural and signalling roles. Their levels and species are modulated by lipases, kinases and phosphatases. This session will focus on PI 3-kinases (PI3Ks), a group of PI kinases that are overactive in most, if not all cancers. PI3Ks generate lipid second messengers that positively control cell proliferation, survival, migration and metabolism. PI3K activation in cancer can occur by overexpression or mutational activation of the PI3Ks themselves and/or by loss-of-function of the phosphatases (such as PTEN and INPP4) that degrade the PI3K lipids. Oncogenic tyrosine kinases and Ras also use PI3Ks as downstream effectors, and resistance to therapy can be mediated by PI3K action. Several PI3K inhibitors are currently in phase I/II trials in various cancers.

The session will showcase fundamental, preclinical and clinical examples of how interference with PI3K biology could be of therapeutic benefit in cancer.