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PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux

Jake S O'Donnell1, Daniela Massi2, Michele W L Teng3

  • 1Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Herston, 4006, Queensland, Australia; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston 4006, Queensland, Australia; School of Medicine, The University of Queensland, Herston 4006, Queensland, Australia.

Seminars in Cancer Biology
|May 4, 2017
PubMed

Insights

Targeting the PI3K-AKT-mTOR pathway with inhibitors impacts cancer cells and host immunity. Combining PI3K-AKT-mTOR inhibitors with immunotherapies may enhance cancer treatment efficacy.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • The PI3K-AKT-mTOR pathway is frequently dysregulated in various cancers, making it a key target for novel therapies.
  • Cancer immunotherapies, such as PD-1/PD-L1 inhibitors, have shown significant clinical success, highlighting the importance of overcoming cancer immunoevasion.
  • Targeting cancer signaling pathways can influence not only tumor cells but also the host immune system and the tumor microenvironment.

Purpose of the Study:

  • To review how PI3K-AKT-mTOR inhibitors affect cancer cell biology, immune cell function, and the tumor microenvironment.
  • To explore the potential of combining PI3K-AKT-mTOR inhibitors with immunotherapies and other targeted therapies for enhanced clinical outcomes.

Main Methods:

  • Literature review of preclinical and clinical studies on PI3K-AKT-mTOR inhibitors.
  • Analysis of the mechanisms by which these inhibitors impact cancer cells and immune components.
  • Evaluation of combination strategies involving PI3K-AKT-mTOR inhibitors and immunotherapies.

Main Results:

  • PI3K-AKT-mTOR inhibitors target cancer cell proliferation and survival pathways.
  • These inhibitors can modulate immune cell function, potentially enhancing anti-tumor immunity.
  • The tumor microenvironment is influenced by PI3K-AKT-mTOR inhibition, affecting immune cell infiltration and activity.

Conclusions:

  • PI3K-AKT-mTOR inhibitors offer a dual approach by targeting cancer cells and modulating the immune system.
  • Rational combinations of PI3K-AKT-mTOR inhibitors with immunotherapies and targeted agents hold promise for improving cancer treatment efficacy.
  • Further research into these combination strategies is warranted to optimize therapeutic benefits in advanced malignancies.
Keywords:
AKTCombination therapyImmunotherapeutic resistanceImmunotherapyInhibitorsPI3KTargeted therapyTumor microenvironmentmTOR

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