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Protein Quality Control Dysfunction in Cardiovascular Complications Induced by Anti-Cancer Drugs

Hai Ying Fu1,2, Mikio Mukai3, Nobuhisa Awata3

  • 1Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Cardiovascular Drugs and Therapy
|January 26, 2017
PubMed

Insights

Anti-cancer drugs can cause heart problems by disrupting protein quality control (PQC). PQC dysfunction is a newly identified mechanism contributing to cardiotoxicity and heart failure in patients undergoing cancer treatment.

Area of Science:

  • Cardiovascular medicine
  • Oncology
  • Molecular biology

Background:

  • Anti-cancer drugs can lead to cardiovascular complications like heart failure and hypertension.
  • Mechanisms such as oxidative stress and mitochondrial dysfunction are implicated in drug-induced cardiotoxicity.
  • Protein quality control (PQC) systems (ER, UPS, autophagy-lysosome) maintain protein homeostasis.

Purpose of the Study:

  • To explore the role of protein quality control (PQC) dysfunction in cardiovascular complications induced by anti-cancer drugs.
  • To highlight PQC as a novel mechanism in cancer drug-related cardiotoxicity.
  • To review the impact of various anti-cancer agents on PQC pathways.

Main Methods:

  • Literature review of studies investigating anti-cancer drug cardiotoxicity.
  • Analysis of evidence linking PQC pathways to cardiac hypertrophy and failure.
  • Examination of specific anti-cancer drug classes and their effects on PQC.

Main Results:

  • PQC dysfunction is identified as a significant contributor to cardiac hypertrophy and heart failure.
  • Several classes of anti-cancer drugs, including TKIs, proteasome inhibitors, anthracyclines, and autophagy inhibitors, impair PQC.
  • Dysfunction in ER, UPS, and autophagy-lysosome systems is linked to cardiotoxicity.

Conclusions:

  • PQC dysfunction represents a critical mechanism underlying cardiovascular complications from anti-cancer therapies.
  • Targeting PQC pathways may offer novel strategies for preventing or treating cardiotoxicity in cancer patients.
  • Further research is warranted to fully elucidate the PQC-drug-heart axis.
Keywords:
Anti-cancer drugsAutophagy-lysosome systemCardiovascular complicationsEndoplasmic reticulumProtein quality controlUbiquitin-proteasome system

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