PI3K and mTOR signaling pathways in cancer: new data on targeted therapies.

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.

journal_name

Curr Oncol Rep

journal_title

Current oncology reports

authors

Willems L,Tamburini J,Chapuis N,Lacombe C,Mayeux P,Bouscary D

doi

10.1007/s11912-012-0227-y

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

129-38

issue

2

eissn

1523-3790

issn

1534-6269

journal_volume

14

pub_type

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