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- Title
Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy.
- Authors
Wander, Seth A.; Hennessy, Bryan T.; Slingerland, Joyce M.
- Abstract
Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.
- Subjects
ENZYME inhibitors; ONCOLOGY; CELLULAR control mechanisms; RAPAMYCIN; DNA damage; CELL proliferation; ANTINEOPLASTIC agents; PROTEIN metabolism; PROTEIN kinase inhibitors; CELLULAR signal transduction; PHOSPHOTRANSFERASES; TRANSCRIPTION factors; TUMORS; CHEMICAL inhibitors; THERAPEUTICS
- Publication
Journal of Clinical Investigation, 2011, Vol 121, Issue 4, p1231
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI44145