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The present and future of PI3K inhibitors for cancer therapy

Pau Castel1, Eneda Toska2,3, Jeffrey A Engelman4

  • 1Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.

Nature Cancer
|February 4, 2022
PubMed

Insights

Phosphoinositide-3- kinase (PI3K) inhibitors are crucial in cancer therapy, targeting cell growth and survival. This review covers their clinical use, mechanisms, and challenges like resistance and toxicity, exploring strategies to enhance efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant phosphoinositide-3-kinase (PI3K) signaling is a common driver of human cancers, impacting cell proliferation, survival, and metabolism.
  • Significant research has led to the development of PI3K inhibitors, progressing from preclinical tools to approved cancer therapeutics.

Purpose of the Study:

  • To review current clinical applications and mechanisms of action for PI3K inhibitors in cancer treatment.
  • To discuss existing limitations, including toxicities and resistance mechanisms associated with PI3K inhibitors.
  • To highlight strategies for improving the efficacy of PI3K-targeted therapies.

Main Methods:

  • Review of clinical trial data for PI3K inhibitors.
  • Analysis of published research on PI3K signaling pathways and inhibitor mechanisms.
  • Examination of preclinical and clinical studies addressing resistance and toxicity.

Main Results:

  • PI3K inhibitors demonstrate clinical utility in various cancers by targeting key oncogenic signaling.
  • Understanding of inhibitor mechanisms of action has advanced significantly.
  • Identified toxicities and resistance pathways pose challenges to widespread clinical success.

Conclusions:

  • PI3K inhibitors represent an important class of targeted cancer therapies.
  • Overcoming resistance and managing toxicities are critical for maximizing therapeutic benefit.
  • Ongoing research into novel strategies holds promise for enhancing PI3K inhibitor efficacy in oncology.

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