Next-generation mTOR inhibitors in clinical oncology: How pathway complexity informs therapeutic strategy

Seth A. Wander, Bryan T. Hennessy, Joyce M. Slingerland

Research output: Contribution to journalReview articlepeer-review

311 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1231-1241
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number4
DOIs
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Medicine(all)

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