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Targeting PI3Kγ in cancer

Giuliana P Mognol1, Anghesom Ghebremedhin1, Judith A Varner2

  • 1Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0819, USA.

Trends in Cancer
|February 13, 2025
PubMed

Insights

Phosphoinositide 3-kinases (PI3K) are crucial in cancer. The unique PI3K-gamma isoform drives myeloid leukemias and immune suppression, presenting a new therapeutic target for aggressive cancers.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Phosphoinositide 3-kinases (PI3Ks) are critical lipid kinases implicated in cancer progression.
  • PI3Ks regulate key cancer cell functions including proliferation, survival, migration, metabolism, and immunity.
  • Numerous PI3K-targeting therapeutics are in clinical development or approved for cancer treatment.

Purpose of the Study:

  • To investigate the role of the class IB PI3K-gamma isoform in myeloid leukemias and antitumor immunity.
  • To evaluate PI3K-gamma as a potential therapeutic target for aggressive leukemias and solid tumors.

Main Methods:

  • Preclinical studies in solid tumors.
  • Clinical trials targeting PI3K-gamma.
  • Analysis of PI3K-gamma expression in myeloid lineage cells and leukemias.

Main Results:

  • PI3K-gamma inhibition enhances antitumor immune responses in preclinical solid tumor models.
  • PI3K-gamma is identified as a driver of acute myeloid leukemia self-renewal.
  • PI3K-gamma is highly expressed in myeloid cells and myeloid leukemias, suggesting a specific role in these malignancies.

Conclusions:

  • PI3K-gamma plays a significant role in tumor immune suppression and myeloid leukemia pathogenesis.
  • Targeting PI3K-gamma represents a promising therapeutic strategy for enhancing anti-tumor immunity and treating aggressive leukemias.
Keywords:
PI3KγPIK3CGacute myeloid leukemia tumor stemnessmyeloid cell traffickingphosphatidylinositol-3 kinasephosphatidylinositol-3 kinase gammaphosphoinositide-3 kinase inhibitorssolid tumor inflammation

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