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PI3K and mTOR inhibitors: a new generation of targeted anticancer agents

Saskia Brachmann1, Christine Fritsch, Saveur-Michel Maira

  • 1Oncology Drug Discovery, Novartis Institutes of Biomedical Research, Basel, Switzerland.

Current Opinion in Cell Biology
|February 10, 2009
PubMed

Insights

The phosphoinosite 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is crucial in human cancers. This review covers PI3K/mTOR inhibitors in clinical trials, discussing combinations, safety, and resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The phosphoinosite 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in human cancer development and progression.
  • Dysregulation of the PI3K/mTOR pathway is frequently observed in various human malignancies, making it a promising therapeutic target.

Purpose of the Study:

  • To review the progress in identifying kinase inhibitors targeting the PI3K and mTOR signaling pathway.
  • To highlight drugs currently in clinical trials for cancer treatment.
  • To discuss potential combination strategies, safety profiles, and resistance mechanisms associated with these novel anticancer agents.

Main Methods:

  • Literature review of epidemiological and experimental studies.
  • Analysis of drug discovery efforts focused on PI3K and mTOR inhibitors.
  • Summary of ongoing clinical trials involving these targeted therapies.

Main Results:

  • Significant advancements have been made in developing PI3K and mTOR kinase inhibitors.
  • Several novel agents targeting this pathway are currently undergoing clinical evaluation.
  • Early data suggests potential for combination therapies, but safety and resistance remain key considerations.

Conclusions:

  • Targeting the PI3K/mTOR pathway represents a promising strategy in cancer therapy.
  • Further research is needed to optimize combination strategies and overcome resistance mechanisms.
  • Careful monitoring of safety profiles is essential for this new class of anticancer drugs.

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