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Targeting phosphoinositide 3-kinase: moving towards therapy

Romina Marone1, Vladimir Cmiljanovic, Bernd Giese

  • 1Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058, Basel, Switzerland.

Biochimica Et Biophysica Acta
|November 13, 2007
PubMed

Insights

Targeting phosphoinositide 3-kinases (PI3K) shows promise for cancer and inflammatory diseases. Isoform-specific PI3K inhibition offers therapeutic potential, but safety concerns and off-target effects require careful consideration for drug development.

Area of Science:

  • Cellular signaling and molecular biology
  • Pharmacology and drug discovery
  • Oncology and immunology

Background:

  • Phosphoinositide 3-kinases (PI3K) are crucial regulators of fundamental cellular processes, including growth, survival, and migration.
  • PI3K pathway dysregulation, through mutations or altered protein levels, is implicated in cancer and inflammatory conditions.
  • Specific PI3K isoforms, like PI3Kgamma and PI3Kdelta, play key roles in immune cell function and inflammatory responses.

Purpose of the Study:

  • To review the disease-relevant functions of isoform-specific PI3K.
  • To analyze the progress of pharmaceutical targeting of the PI3K pathway.
  • To discuss safety concerns associated with PI3K inhibitors.

Main Methods:

  • Literature review of PI3K pathway deregulation in disease.
  • Analysis of genetic targeting studies in mouse models.
  • Review of over 400 patents related to pharmaceutical targeting of PI3K.

Main Results:

  • PI3K pathway deregulation is linked to cancer cell proliferation.
  • Isoform-specific PI3K targeting has shown efficacy in preclinical models of rheumatoid arthritis and lupus erythematosus.
  • Several PI3K pathway inhibitors are in early-phase clinical trials for cancer and myocardial infarction.

Conclusions:

  • Targeting the PI3K pathway holds significant therapeutic potential for various diseases.
  • Isoform-specific inhibition is a key strategy, but requires careful management of safety concerns.
  • Ongoing clinical trials indicate progress in translating PI3K-targeted therapies.

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