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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
Summary
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 inflammationMore Related Videos
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