title: Benefits of mTOR kinase targeting in oncology: pre-clinical evidence with AZD8055.
abstract: AZD8055 is a small-molecule inhibitor of mTOR (mammalian target of rapamycin) kinase activity. The present review highlights molecular and phenotypic differences between AZD8055 and allosteric inhibitors of mTOR such as rapamycin. Biomarkers, some of which are applicable to clinical studies, as well as biological effects such as autophagy, growth inhibition and cell death are compared between AZD8055 and rapamycin. Potential ways to develop rational combinations with mTOR kinase inhibitors are also discussed. Overall, AZD8055 may provide a better therapeutic strategy than rapamycin and analogues.
authors.affiliation: Oncology iMed, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: Gayle
authors.initials: G
authors.lastname: Marshall
authors.forename: Zoe
authors.initials: Z
authors.lastname: Howard
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dry
authors.forename: Sarah
authors.initials: S
authors.lastname: Fenton
authors.forename: Dan
authors.initials: D
authors.lastname: Heathcote
authors.forename: Neil
authors.initials: N
authors.lastname: Gray
authors.forename: Heather
authors.initials: H
authors.lastname: Keen
authors.forename: Armelle
authors.initials: A
authors.lastname: Logie
authors.forename: Sarah
authors.initials: S
authors.lastname: Holt
authors.forename: Paul
authors.initials: P
authors.lastname: Smith
authors.forename: Sylvie M
authors.initials: SM
authors.lastname: Guichard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008495:Medical Oncology / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000379:methods; D009025:Morpholines / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D009025:Morpholines; D047428:Protein Kinase Inhibitors; C546624:(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus