Precision Cardio-Oncology: a Systems-Based Perspective on Cardiotoxicity of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors

J Cardiovasc Transl Res. 2020 Jun;13(3):402-416. doi: 10.1007/s12265-020-09992-5. Epub 2020 Apr 6.

Abstract

Cancer therapies have been evolving from conventional chemotherapeutics to targeted agents. This has fulfilled the hope of greater efficacy but unfortunately not of greater safety. In fact, a broad spectrum of toxicities can be seen with targeted therapies, including cardiovascular toxicities. Among these, cardiomyopathy and heart failure have received greatest attention, given their profound implications for continuation of cancer therapies and cardiovascular morbidity and mortality. Prediction of risk has always posed a challenge and even more so with the newer targeted agents. The merits of accurate risk prediction, however, are very evident, e.g. facilitating treatment decisions even before the first dose is given. This is important for agents with a long half-life and high potential to induced life-threatening cardiac complications, such as myocarditis with immune checkpoint inhibitors. An opportunity to address these needs in the field of cardio-oncology is provided by the expanding repertoire of "-omics" and other tools in precision medicine and their integration in a systems biology approach. This may allow for new insights into patho-mechanisms and the creation of more precise and cost-effective risk prediction tools with the ultimate goals of improved therapy decisions and prevention of cardiovascular complications. Herein, we explore this topic as a future approach to translating the complexity of cardio-oncology to the reality of patient care.

Keywords: Cancer; Cardiotoxicity; Immune checkpoints; Precision medicine; Systems biology; Tyrosine kinases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / adverse effects*
  • Cancer Survivors*
  • Cardiology*
  • Cardiotoxicity
  • Heart Diseases / chemically induced*
  • Heart Diseases / genetics
  • Heart Diseases / metabolism
  • Humans
  • Medical Oncology*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / immunology
  • Precision Medicine*
  • Protein Kinase Inhibitors / adverse effects*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Risk Assessment
  • Risk Factors
  • Systems Biology*

Substances

  • Antineoplastic Agents, Immunological
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases