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Updated: Jan 5, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

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Management of toxicity to isoform α-specific PI3K inhibitors

S E Nunnery1, I A Mayer1

  • 1Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, USA.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|October 19, 2019
PubMed

Insights

PI3K/AKT pathway inhibitors are crucial for cancer treatment but cause side effects like hyperglycemia and rash. Proactive management and patient education are key to improving quality of life and treatment efficacy.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Alterations in the phosphoinositide 3-kinase (PI3K)/AKT pathway are prevalent in various cancers, particularly breast cancer (70% of tumors).
  • Hyperactivation of the PI3K/AKT pathway is a common driver in cancer development and progression.
  • PI3K pathway inhibitors represent a targeted therapeutic strategy for cancer control.

Purpose of the Study:

  • To address the challenges associated with PI3K/AKT pathway inhibitor toxicity.
  • To highlight the impact of side effects on patient quality of life and treatment efficacy.
  • To propose strategies for proactive management of PI3K inhibitor-related toxicities.

Main Methods:

  • Review of current literature on PI3K/AKT pathway inhibitors and their associated toxicities.
  • Analysis of common side effects, including hyperglycemia, rash, stomatitis, diarrhea, nausea, and fatigue.
  • Discussion of the reversibility of side effects and the role of drug half-life.

Main Results:

  • PI3K/AKT pathway inhibitors frequently cause on-target and off-target toxicities.
  • Reported side effects often necessitate dose reductions, treatment delays, or discontinuation.
  • Most toxicities are reversible with early intervention and drug interruption due to short drug half-lives.

Conclusions:

  • Effective management of PI3K/AKT pathway inhibitors requires an interdisciplinary approach.
  • Comprehensive patient education regarding potential toxicities is essential.
  • Proactive strategies, including frequent monitoring and early intervention, can mitigate side effects and improve treatment outcomes.
Keywords:
PI3K inhibitorssupportive caretoxicities

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