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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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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
|January 14, 2020
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, notably 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 challenge of toxicity associated with PI3K/AKT pathway inhibitors.
  • 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 toxicities.
  • Analysis of common on-target and off-target side-effects.
  • Evaluation of management strategies for drug-induced toxicities.

Main Results:

  • PI3K/AKT pathway inhibitors commonly cause reversible side-effects including hyperglycemia, rash, stomatitis, diarrhea, nausea, and fatigue.
  • These toxicities frequently lead to dose reductions, treatment delays, and discontinuation, impairing treatment efficacy and quality of life.
  • Most side-effects are manageable with early intervention due to the short half-life of these drugs.

Conclusions:

  • An interdisciplinary and proactive approach is essential for managing patients on PI3K pathway inhibitors.
  • Comprehensive patient education, frequent monitoring, and early intervention are crucial for mitigating side-effects.
  • Prophylactic strategies should be integrated into patient management to optimize treatment outcomes and patient well-being.
Keywords:
PI3K inhibitorssupportive caretoxicities

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