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AMPK activation; a potential strategy to mitigate TKI-induced cardiovascular toxicity

Nasser Safaie1, Gholamreza Idari2, Diba Ghasemi3

  • 1Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Archives of Physiology and Biochemistry
|November 11, 2024
PubMed

Insights

AMP-activated protein kinase (AMPK) activation may mitigate cardiovascular toxicity caused by Tyrosine Kinase Inhibitors (TKIs) in cancer therapy. This finding offers potential for safer, personalized cancer treatments while preserving heart health.

Area of Science:

  • Cardiovascular Pharmacology
  • Oncology
  • Molecular Signaling

Background:

  • Tyrosine Kinase Inhibitors (TKIs) have transformed cancer treatment but are associated with significant cardiovascular toxicity.
  • Understanding the mechanisms underlying TKI-induced cardiotoxicity is crucial for patient safety and treatment efficacy.
  • AMP-activated protein kinase (AMPK) is a key cellular energy sensor with known roles in cardiovascular health.

Purpose of the Study:

  • To investigate the intricate relationship between AMP-activated protein kinase (AMPK) signaling and Tyrosine Kinase Inhibitor (TKI)-induced cardiovascular toxicity.
  • To determine if AMPK activation can serve as a strategic target for mitigating adverse cardiovascular effects associated with TKIs.
  • To explore the potential of AMPK activation in developing safer, personalized anticancer therapies.

Main Methods:

  • Exploration of existing literature and mechanistic studies on TKI-induced cardiotoxicity.
  • Analysis of the role of AMPK signaling pathways in cardiovascular homeostasis and response to cellular stress.
  • Review of preclinical and clinical data investigating the impact of AMPK modulators on TKI-related cardiovascular adverse events.

Main Results:

  • Evidence suggests a complex interplay where AMPK activation may counteract TKI-induced cellular damage in the cardiovascular system.
  • AMPK signaling appears to influence key pathways involved in cardiac metabolism, inflammation, and cell survival, potentially offering cardioprotection.
  • Modulating AMPK activity presents a promising avenue for managing TKI-associated cardiovascular risks.

Conclusions:

  • AMPK activation holds significant potential as a therapeutic strategy to alleviate cardiovascular toxicity induced by Tyrosine Kinase Inhibitors.
  • Targeting AMPK could enable a better balance between effective cancer treatment and the preservation of cardiovascular well-being.
  • Further research into AMPK modulation is warranted to advance personalized oncology and improve patient outcomes.
Keywords:
AMPKNrf2SIRT1cardiovascular toxicitytyrosine kinase inhibitors

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