Current Oncology Reports

, Volume 14, Issue 2, pp 129–138

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

  • Lise Willems
  • Jerome Tamburini
  • Nicolas Chapuis
  • Catherine Lacombe
  • Patrick Mayeux
  • Didier Bouscary
Evolving Therapies (RM Bukowski, Section Editor)

DOI: 10.1007/s11912-012-0227-y

Cite this article as:
Willems, L., Tamburini, J., Chapuis, N. et al. Curr Oncol Rep (2012) 14: 129. doi:10.1007/s11912-012-0227-y

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.

Keywords

mTORC1 mTORC2 Cancer PI3K AKT Targeted therapies TORKinib Dual PI3K/AKT inhibitors 

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Lise Willems
    • 1
    • 2
  • Jerome Tamburini
    • 1
    • 2
  • Nicolas Chapuis
    • 1
    • 3
  • Catherine Lacombe
    • 1
    • 3
  • Patrick Mayeux
    • 1
  • Didier Bouscary
    • 1
    • 2
    • 4
  1. 1.Institut CochinUniversité Paris DescartesParisFrance
  2. 2.Service de Médecine Interne-UF d’HématologieHôpital Cochin, AP-HPParisFrance
  3. 3.Service d’Hématologie BiologiqueHôpital Cochin, AP-HPParisFrance
  4. 4.Institut CochinParisFrance