The Impact of Pazopanib on the Cardiovascular System

Cody N. Justice, Mohamed H. Derbala, Tesla M. Baich, Amber N. Kempton, Aaron S. Guo, Thai H Ho, Sakima A. Smith

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown. Gaining a deeper understanding of these mechanisms is essential for the development of appropriate surveillance strategies and possible diagnostic biomarkers to allow us to monitor patients and modulate therapy prior to significant cardiac insult. This approach will be vital in keeping patients on these life-saving therapies and may be applicable to other tyrosine kinase inhibitors as well. In this review, we provide a comprehensive overview of the preclinical and clinical side effects of pazopanib with a focus on the mechanisms responsible for its toxicity to the cardiovascular system.

Original languageEnglish (US)
Pages (from-to)387-398
Number of pages12
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume23
Issue number5
DOIs
StatePublished - Sep 1 2018

Fingerprint

Cardiovascular System
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor Receptor
Therapeutics
Renal Cell Carcinoma
Sarcoma
Biomarkers
Hypertension
pazopanib

Keywords

  • hypertension
  • pazopanib
  • renal cell carcinoma
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

Justice, C. N., Derbala, M. H., Baich, T. M., Kempton, A. N., Guo, A. S., Ho, T. H., & Smith, S. A. (2018). The Impact of Pazopanib on the Cardiovascular System. Journal of Cardiovascular Pharmacology and Therapeutics, 23(5), 387-398. https://doi.org/10.1177/1074248418769612

The Impact of Pazopanib on the Cardiovascular System. / Justice, Cody N.; Derbala, Mohamed H.; Baich, Tesla M.; Kempton, Amber N.; Guo, Aaron S.; Ho, Thai H; Smith, Sakima A.

In: Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 23, No. 5, 01.09.2018, p. 387-398.

Research output: Contribution to journalReview article

Justice, CN, Derbala, MH, Baich, TM, Kempton, AN, Guo, AS, Ho, TH & Smith, SA 2018, 'The Impact of Pazopanib on the Cardiovascular System', Journal of Cardiovascular Pharmacology and Therapeutics, vol. 23, no. 5, pp. 387-398. https://doi.org/10.1177/1074248418769612
Justice, Cody N. ; Derbala, Mohamed H. ; Baich, Tesla M. ; Kempton, Amber N. ; Guo, Aaron S. ; Ho, Thai H ; Smith, Sakima A. / The Impact of Pazopanib on the Cardiovascular System. In: Journal of Cardiovascular Pharmacology and Therapeutics. 2018 ; Vol. 23, No. 5. pp. 387-398.
@article{2f1653ecbf314a16b1179faedd39c259,
title = "The Impact of Pazopanib on the Cardiovascular System",
abstract = "Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown. Gaining a deeper understanding of these mechanisms is essential for the development of appropriate surveillance strategies and possible diagnostic biomarkers to allow us to monitor patients and modulate therapy prior to significant cardiac insult. This approach will be vital in keeping patients on these life-saving therapies and may be applicable to other tyrosine kinase inhibitors as well. In this review, we provide a comprehensive overview of the preclinical and clinical side effects of pazopanib with a focus on the mechanisms responsible for its toxicity to the cardiovascular system.",
keywords = "hypertension, pazopanib, renal cell carcinoma, tyrosine kinase inhibitors",
author = "Justice, {Cody N.} and Derbala, {Mohamed H.} and Baich, {Tesla M.} and Kempton, {Amber N.} and Guo, {Aaron S.} and Ho, {Thai H} and Smith, {Sakima A.}",
year = "2018",
month = "9",
day = "1",
doi = "10.1177/1074248418769612",
language = "English (US)",
volume = "23",
pages = "387--398",
journal = "Journal of Cardiovascular Pharmacology and Therapeutics",
issn = "1074-2484",
publisher = "SAGE Publications Ltd",
number = "5",

}

TY - JOUR

T1 - The Impact of Pazopanib on the Cardiovascular System

AU - Justice, Cody N.

AU - Derbala, Mohamed H.

AU - Baich, Tesla M.

AU - Kempton, Amber N.

AU - Guo, Aaron S.

AU - Ho, Thai H

AU - Smith, Sakima A.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown. Gaining a deeper understanding of these mechanisms is essential for the development of appropriate surveillance strategies and possible diagnostic biomarkers to allow us to monitor patients and modulate therapy prior to significant cardiac insult. This approach will be vital in keeping patients on these life-saving therapies and may be applicable to other tyrosine kinase inhibitors as well. In this review, we provide a comprehensive overview of the preclinical and clinical side effects of pazopanib with a focus on the mechanisms responsible for its toxicity to the cardiovascular system.

AB - Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown. Gaining a deeper understanding of these mechanisms is essential for the development of appropriate surveillance strategies and possible diagnostic biomarkers to allow us to monitor patients and modulate therapy prior to significant cardiac insult. This approach will be vital in keeping patients on these life-saving therapies and may be applicable to other tyrosine kinase inhibitors as well. In this review, we provide a comprehensive overview of the preclinical and clinical side effects of pazopanib with a focus on the mechanisms responsible for its toxicity to the cardiovascular system.

KW - hypertension

KW - pazopanib

KW - renal cell carcinoma

KW - tyrosine kinase inhibitors

UR - http://www.scopus.com/inward/record.url?scp=85051794110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051794110&partnerID=8YFLogxK

U2 - 10.1177/1074248418769612

DO - 10.1177/1074248418769612

M3 - Review article

C2 - 29706106

AN - SCOPUS:85051794110

VL - 23

SP - 387

EP - 398

JO - Journal of Cardiovascular Pharmacology and Therapeutics

JF - Journal of Cardiovascular Pharmacology and Therapeutics

SN - 1074-2484

IS - 5

ER -