PI3K and MTOR Signaling Pathways in Cancer: New Data on Targeted Therapies

Overview

Journal Curr Oncol Rep

Publisher Current Science

Specialty Oncology

Date 2012 Feb 22

PMID 22350330

Citations 108

Authors

Lise Willems

Jerome Tamburini

Nicolas Chapuis

Catherine Lacombe

Patrick Mayeux

Didier Bouscary

Affiliations

Soon will be listed here.

Abstract

The mammalian target of rapamycin (mTOR) and the phosphoinositide 3-kinase (PI3K) signaling pathways are commonly deregulated in cancers and promote cellular growth, proliferation, and survival. mTOR is part of two complexes, mTORC1 and mTORC2, with different biochemical structures and substrates specificity. PI3K/AKT activation may result from genetic hits affecting different components of the pathway, whereas the mechanisms leading to constitutive mTORC1 activation remain globally unknown. The connections between the PI3K and mTOR kinases are multiple and complex, including common substrates, negative feedback loops, or direct activation mechanisms. First-generation allosteric mTOR inhibitors (eg, rapamycin) are mainly active on mTORC1 and mostly display cytostatic anti-tumor activity. Recently, second-generation catalytic mTOR inhibitors targeting both mTOR complexes 1 and 2 have been developed. Some of them also inhibit class IA PI3K. Here, we highlight recent data generated with these new inhibitors against cancer cells and their potential as anti-cancer drugs.

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