Heart Failure With Targeted Cancer Therapies: Mechanisms and Cardioprotection

Circ Res. 2021 May 14;128(10):1576-1593. doi: 10.1161/CIRCRESAHA.121.318223. Epub 2021 May 13.

Abstract

Oncology has seen growing use of newly developed targeted therapies. Although this has resulted in dramatic improvements in progression-free and overall survival, challenges in the management of toxicities related to longer-term treatment of these therapies have also become evident. Although a targeted approach often exploits the differences between cancer cells and noncancer cells, overlap in signaling pathways necessary for the maintenance of function and survival in multiple cell types has resulted in systemic toxicities. In particular, cardiovascular toxicities are of important concern. In this review, we highlight several targeted therapies commonly used across a variety of cancer types, including HER2 (human epidermal growth factor receptor 2)+ targeted therapies, tyrosine kinase inhibitors, immune checkpoint inhibitors, proteasome inhibitors, androgen deprivation therapies, and MEK (mitogen-activated protein kinase kinase)/BRAF (v-raf murine sarcoma viral oncogene homolog B) inhibitors. We present the oncological indications, heart failure incidence, hypothesized mechanisms of cardiotoxicity, and potential mechanistic rationale for specific cardioprotective strategies.

Keywords: cardiotoxicity; heart failure; incidence; survival; tyrosine.

Publication types

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

MeSH terms

  • Androgen Antagonists / adverse effects
  • Anthracyclines / adverse effects
  • Antineoplastic Agents, Immunological / adverse effects
  • Cardiotonic Agents / therapeutic use
  • Cardiotoxicity / etiology
  • Cardiotoxicity / prevention & control
  • Heart Failure / chemically induced*
  • Heart Failure / epidemiology
  • Heart Failure / prevention & control
  • Humans
  • Immunotherapy / adverse effects
  • Incidence
  • Molecular Targeted Therapy / adverse effects*
  • Neoplasms / drug therapy*
  • Proteasome Inhibitors / adverse effects
  • Protein Kinase Inhibitors / adverse effects

Substances

  • Androgen Antagonists
  • Anthracyclines
  • Antineoplastic Agents, Immunological
  • Cardiotonic Agents
  • Proteasome Inhibitors
  • Protein Kinase Inhibitors