Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway.

Journal Article (Journal Article;Review)

The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway controls many cellular processes that are important for the formation and progression of cancer, including apoptosis, transcription, translation, metabolism, angiogenesis, and cell cycle progression. Genetic alterations and biochemical activation of the pathway are frequent events in preneoplastic lesions and advanced cancers and often portend a poor prognosis. Thus, inhibition of the PI3K/Akt/mTOR pathway is an attractive concept for cancer prevention and/or therapy. Inhibitors of individual components, such as PI3K, PDK-1, Akt, and mTOR, are being developed at a rapid pace and have promise for improving the care of cancer patients. Here, we review the published data on inhibitors of the pathway and discuss relevant issues, such as the complex regulation of the pathway, the design of clinical trials, and the likelihood of finding a therapeutic index when targeting such a critical signaling pathway.

Full Text

Duke Authors

Cited Authors

  • Granville, CA; Memmott, RM; Gills, JJ; Dennis, PA

Published Date

  • February 1, 2006

Published In

Volume / Issue

  • 12 / 3 Pt 1

Start / End Page

  • 679 - 689

PubMed ID

  • 16467077

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-05-1654

Language

  • eng

Conference Location

  • United States