Benefits of mTOR kinase targeting in oncology: pre-clinical evidence with AZD8055 |
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Authors: | Marshall Gayle Howard Zoe Dry Jonathan Fenton Sarah Heathcote Dan Gray Neil Keen Heather Logie Armelle Holt Sarah Smith Paul Guichard Sylvie M |
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Affiliation: | Oncology iMed, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. |
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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. |
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