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Targeting PI3 kinase/AKT/mTOR signaling in cancer

Karen Sheppard1, Kathryn M Kinross, Benjamin Solomon

  • 1Division of Cancer Research, Peter MacCallum Cancer Centre, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.

Critical Reviews in Oncogenesis
|April 5, 2012
PubMed

Insights

The phosphatidylinositol 3 kinase (PI3K) pathway is crucial for cell functions and frequently hyperactivated in cancer. Targeting PI3K in clinical trials shows promise for cancer treatment with good tolerability.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The phosphatidylinositol 3 kinase (PI3K) pathway regulates critical cellular processes including growth, proliferation, metabolism, survival, and angiogenesis.
  • Hyperactivation of the PI3K pathway is a common event in human cancers, making it a significant therapeutic target.
  • Numerous novel compounds targeting the PI3K pathway are currently under investigation in extensive clinical trials for cancer treatment.

Purpose of the Study:

  • To review the PI3K pathway's interactions with other signaling cascades.
  • To highlight mechanisms driving PI3K pathway hyperactivation in cancer.
  • To discuss current and potential therapeutic strategies targeting the PI3K pathway in clinical trials.

Main Methods:

  • Literature review of preclinical and clinical data on PI3K pathway inhibitors.
  • Analysis of signaling network interactions and hyperactivation mechanisms.
  • Evaluation of patient selection and combination therapy strategies based on existing data.

Main Results:

  • PI3K pathway hyperactivation is a frequent hallmark of human cancers.
  • A large number of PI3K-targeting agents are in over 150 cancer-related clinical trials.
  • Clinical trial data suggest that PI3K inhibitors are generally well-tolerated.

Conclusions:

  • The PI3K pathway is a validated and actively pursued target in oncology.
  • Current clinical trials demonstrate the feasibility and tolerability of PI3K-targeted therapies.
  • Future directions include optimizing patient selection and exploring combination therapies for enhanced efficacy.

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