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Targeting PI3K in cancer: mechanisms and advances in clinical trials

Jing Yang1, Ji Nie1, Xuelei Ma1

  • 1Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Molecular Cancer
|February 21, 2019
PubMed

Insights

Targeting the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is crucial for cancer treatment. This review covers PI3K inhibitors, their clinical trials, and resistance mechanisms.

Area of Science:

  • Molecular Biology
  • Oncology
  • Pharmacology

Background:

  • The Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is a critical regulator of cellular processes and a key player in cancer development.
  • Dysregulation of this pathway is frequently observed in various types of cancer, making it a significant therapeutic target.

Purpose of the Study:

  • To critically review the role of the PI3K pathway in tumor progression.
  • To summarize the development of PI3K inhibitors based on current clinical trial evaluations.
  • To elucidate the mechanisms of resistance that arise in response to PI3K inhibition.

Main Methods:

  • Comprehensive literature review of scientific publications and clinical trial data.
  • Analysis of the PI3K/AKT/mTOR pathway's involvement in oncogenesis.
  • Categorization and evaluation of different classes of PI3K inhibitors (dual PI3K/mTOR, pan-PI3K, isoform-specific).

Main Results:

  • PI3K inhibitors have demonstrated efficacy in inhibiting tumor progression across various preclinical and clinical studies.
  • Numerous PI3K-targeting drugs are progressing through clinical trials, indicating a growing therapeutic landscape.
  • Understanding resistance mechanisms is vital for optimizing treatment strategies and overcoming therapeutic limitations.

Conclusions:

  • The PI3K/AKT/mTOR pathway remains a central focus for cancer therapy development.
  • Ongoing clinical trials are evaluating the efficacy and safety of diverse PI3K inhibitors.
  • Addressing resistance mechanisms is paramount for the successful clinical application of PI3K-targeted therapies.
Keywords:
CancerPI3KTarget therapymTOR

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