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Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems-Based Approaches

S-A Brown1, L Nhola1, J Herrmann1

  • 1Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.

Clinical Pharmacology and Therapeutics
|November 3, 2016
PubMed

Insights

Cancer therapies like tyrosine kinase inhibitors (TKIs) can cause cardiovascular side effects. This study explores TKI-induced heart issues and suggests systems medicine for personalized patient care.

Area of Science:

  • Oncology
  • Cardiology
  • Pharmacology

Background:

  • Cancer is increasingly a chronic condition, with therapy side effects becoming significant.
  • Small molecule tyrosine kinase inhibitors (TKIs) are crucial cancer treatments.
  • Cardiovascular toxicities are common adverse effects of TKIs, including hypertension and heart failure.

Purpose of the Study:

  • To elucidate the mechanisms of TKI-induced cardiovascular toxicity.
  • To explore systems-based approaches for understanding these toxicities.
  • To recommend implementing systems medicine for cardiovascular wellness post-cancer therapy.

Main Methods:

  • Review of TKI mechanisms and cardiovascular side effects.
  • Analysis of intracellular signaling pathways involved in cardiotoxicity.
  • Illustration of synergistic cardiotoxicity from combined therapies (TKIs, anthracyclines, monoclonal antibodies).

Main Results:

  • TKIs induce cardiovascular toxicities such as hypertension, heart failure, QTc prolongation, and premature coronary heart disease.
  • Understanding intracellular signaling is key to TKI cardiotoxicity.
  • Combined therapies can lead to synergistic cardiovascular damage.

Conclusions:

  • TKI-induced cardiovascular toxicity is a significant clinical concern.
  • Systems-based approaches and systems medicine are vital for managing cardiotoxicity.
  • Personalized cardiovascular care strategies are recommended for cancer survivors.

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