title: 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.
authors.affiliation: Institut Cochin, Université Paris Descartes, CNRS UMR8104, Paris Inserm, U1016, Paris, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Willems
authors.forename: Jerome
authors.initials: J
authors.lastname: Tamburini
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chapuis
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacombe
authors.forename: Patrick
authors.initials: P
authors.lastname: Mayeux
authors.forename: Didier
authors.initials: D
authors.lastname: Bouscary
mesh_terms: D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D058990:Molecular Targeted Therapy / Q000379:methods*; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011506:Proteins; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; C493245:CRTC2 protein, human