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A targeted approach to phosphoinositide-3-kinase/Akt/mammalian target of rapamycin-induced hyperglycemia

Yee-Ming Melody Cheung1, Marie McDonnell2, Ole-Petter Riksfjord Hamnvik2

  • 1Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Medicine, Endocrine Unit, Austin Hospital, The University of Melbourne, Victoria, Australia.

Current Problems in Cancer
|August 11, 2021
PubMed

Insights

New cancer drugs targeting the PI3K/Akt/mTOR pathway can cause hyperglycemia. Updated guidelines are needed to manage this common side effect in cancer patients receiving prolonged treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Endocrinology

Background:

  • Phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway inhibitors are novel antineoplastic agents used in cancer treatment.
  • Increased cancer survival leads to longer exposure to these therapies, necessitating a focus on adverse effects.
  • The PI3K/Akt/mTOR pathway regulates cellular growth and insulin metabolism, making hyperglycemia and insulin resistance common side effects.

Purpose of the Study:

  • To review the incidence and mechanisms of hyperglycemia induced by PI3K/Akt/mTOR inhibitors.
  • To provide an updated management strategy for PI3K/Akt/mTOR inhibitor-induced hyperglycemia.
  • To address the lack of recent consensus guidelines for managing this adverse effect.

Main Methods:

  • Comprehensive literature review on PI3K/Akt/mTOR inhibitors and hyperglycemia.
  • Analysis of current understanding of hyperglycemia induction pathways.
  • Development of a proposed management strategy based on updated evidence.

Main Results:

  • Hyperglycemia and insulin resistance are frequently reported adverse effects of PI3K/Akt/mTOR inhibitors.
  • Existing guidelines for managing hyperglycemia are outdated, predating many current agents.
  • A detailed summary of agent-specific hyperglycemia incidence and mechanisms is presented.

Conclusions:

  • Updated management strategies are crucial for PI3K/Akt/mTOR inhibitor-induced hyperglycemia due to increased patient survival and new therapeutic agents.
  • The review provides a comprehensive overview of the literature and a proposed approach to facilitate clinical management.
  • Effective management of hyperglycemia is essential for this complex oncological patient population.
Keywords:
Akt inhibitorDiabetesHyperglycemiaPI3K inhibitormTOR inhibitor

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