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

  • Evolving Therapies (RM Bukowski, Section Editor)
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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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Authors and Affiliations

  1. Institut Cochin, Université Paris Descartes, CNRS UMR8104, Paris Inserm, U1016, Paris, France

    Lise Willems, Jerome Tamburini, Nicolas Chapuis, Catherine Lacombe, Patrick Mayeux & Didier Bouscary

  2. Service de Médecine Interne-UF d’Hématologie, Hôpital Cochin, AP-HP, Paris, France

    Lise Willems, Jerome Tamburini & Didier Bouscary

  3. Service d’Hématologie Biologique, Hôpital Cochin, AP-HP, Paris, France

    Nicolas Chapuis & Catherine Lacombe

  4. Institut Cochin, 27 rue du faubourg Saint Jacques, 75014, Paris, France

    Didier Bouscary

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  1. Lise Willems
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  2. Jerome Tamburini
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  3. Nicolas Chapuis
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  4. Catherine Lacombe
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Correspondence to Didier Bouscary.

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Willems, L., Tamburini, J., Chapuis, N. et al. PI3K and mTOR Signaling Pathways in Cancer: New Data on Targeted Therapies. Curr Oncol Rep 14, 129–138 (2012). https://doi.org/10.1007/s11912-012-0227-y

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