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Present and future of PI3K pathway inhibition in cancer: perspectives and limitations

E Ciraolo1, F Morello, E Hirsch

  • 1Department of Genetics, Biology and Biochemistry, Molecular Biotecnology Center, University of Torino, Torino, Italy.

Current Medicinal Chemistry
|June 9, 2011
PubMed

Insights

Phosphoinositide 3-kinases (PI3Ks) are crucial in cancer. Inhibitors targeting PI3Ks and mTOR show promise in clinical trials for cancer therapy, with ongoing research into their efficacy and side effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Phosphoinositide 3-kinases (PI3Ks) regulate critical signaling pathways involved in cancer cell proliferation, survival, motility, and angiogenesis.
  • Aberrant PI3K pathway activation, due to mutations or overexpression, is common in various human cancers.

Purpose of the Study:

  • To summarize the pharmacology and preliminary clinical data of PI3K inhibitors currently in clinical trials for cancer therapy.
  • To review preclinical findings on the systemic effects of PI3K inhibition on non-cancer tissues, identifying potential side effects and limitations.

Main Methods:

  • Review of pharmacological data for PI3K inhibitors.
  • Analysis of preliminary clinical trial results.
  • Examination of preclinical studies on systemic PI3K inhibition effects.

Main Results:

  • Several small molecule inhibitors targeting PI3Ks and/or mTOR are in clinical trials.
  • These inhibitors include pan-class I, isoform-selective, and dual PI3K/mTOR inhibitors.
  • Preclinical studies highlight potential on-target toxicities in non-cancer tissues.

Conclusions:

  • PI3K inhibitors represent a promising class of novel cancer therapeutics.
  • Understanding the pharmacology and clinical data is essential for optimizing their use.
  • Careful consideration of potential side effects is necessary for safe and effective PI3K blockade in patients.

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