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

Publication ,  Journal Article
Granville, CA; Memmott, RM; Gills, JJ; Dennis, PA
Published in: Clin Cancer Res
February 1, 2006

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.

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Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

February 1, 2006

Volume

12

Issue

3 Pt 1

Start / End Page

679 / 689

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Structure-Activity Relationship
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Protein Kinase Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase
 

Citation

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Granville, C. A., Memmott, R. M., Gills, J. J., & Dennis, P. A. (2006). Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway. Clin Cancer Res, 12(3 Pt 1), 679–689. https://doi.org/10.1158/1078-0432.CCR-05-1654
Granville, Courtney A., Regan M. Memmott, Joell J. Gills, and Phillip A. Dennis. “Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway.Clin Cancer Res 12, no. 3 Pt 1 (February 1, 2006): 679–89. https://doi.org/10.1158/1078-0432.CCR-05-1654.
Granville CA, Memmott RM, Gills JJ, Dennis PA. Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):679–89.
Granville, Courtney A., et al. “Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway.Clin Cancer Res, vol. 12, no. 3 Pt 1, Feb. 2006, pp. 679–89. Pubmed, doi:10.1158/1078-0432.CCR-05-1654.
Granville CA, Memmott RM, Gills JJ, Dennis PA. Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):679–689.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

February 1, 2006

Volume

12

Issue

3 Pt 1

Start / End Page

679 / 689

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Structure-Activity Relationship
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Protein Kinase Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase