1. Benefits of mTOR kinase targeting in oncology: pre-clinical evidence with AZD8055
- Author
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Sylvie Guichard, Dan Heathcote, Neil Gray, Sarah V. Holt, Zoe Howard, Jonathan R. Dry, Heather Keen, Paul D. Smith, Sarah Fenton, Armelle Logie, and Gayle Marshall
- Subjects
Sirolimus ,Programmed cell death ,Kinase ,Morpholines ,TOR Serine-Threonine Kinases ,Autophagy ,RPTOR ,Drug Evaluation, Preclinical ,Antineoplastic Agents ,Pharmacology ,Biology ,Medical Oncology ,Biochemistry ,Neoplasms ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Kinase activity ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,medicine.drug - 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.
- Published
- 2011
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