Contribution of membrane transporters to chemotherapy-induced cardiotoxicity

Basic Clin Pharmacol Toxicol. 2022 Jan:130 Suppl 1:36-47. doi: 10.1111/bcpt.13635. Epub 2021 Jul 21.

Abstract

Membrane transporters play a key role in determining the pharmacokinetic profile, therapeutic safety, and efficacy of many chemotherapeutic drugs by regulating cellular influx and efflux. Rapidly emerging evidence has shown that tissue-specific expression of transporters contributes to local drug accumulation and drug-drug interactions and that functional alterations in these transporters can directly influence an individual's susceptibility to drug-induced toxicity. Comprehending the complex mechanism of transporter function in regulating drug distribution in tissues, such as the heart, is necessary in order to acquire novel therapeutic strategies aimed at evading unwanted drug accumulation and toxicities and to ameliorate the safety of current therapeutic regimens. Here, we provide an overview of membrane transporters with a role in chemotherapy-induced cardiotoxicity and discuss novel strategies to improve therapeutic outcomes.

Keywords: ABC transporters; cardiotoxicity; chemotherapy; solute carriers.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacokinetics
  • Biological Transport
  • Cardiotoxicity / etiology*
  • Cardiotoxicity / physiopathology
  • Drug Interactions
  • Humans
  • Membrane Transport Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • Membrane Transport Proteins