Oncotarget

Research Perspectives:

Bruton’s tyrosine kinase inhibitor-related cardiotoxicity: The quest for predictive biomarkers and improved risk stratification

Jai N. Patel, Jai Singh and Nilanjan Ghosh _

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Oncotarget. 2024; 15:355-359. https://doi.org/10.18632/oncotarget.28589

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Abstract

Jai N. Patel1,2, Jai Singh3 and Nilanjan Ghosh2,4

1 Department of Cancer Pharmacology and Pharmacogenomics, Atrium Health Levine Cancer Institute, Charlotte, NC 28204, USA

2 Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA

3 Sanger Heart and Vascular Institute, Atrium Health, Charlotte, NC 28204, USA

4 Department of Hematologic Malignancies and Blood Disorders, Atrium Health Levine Cancer Institute, Charlotte, NC 28204, USA

Correspondence to:

Nilanjan Ghosh, email: [email protected]

Keywords: BTK inhibitor; cardiotoxicity; biomarkers; risk; genetics

Received: May 13, 2024     Accepted: May 21, 2024     Published: June 03, 2024

Copyright: © 2024 Patel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Ibrutinib was the first Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment of patients with chronic lymphocytic leukemia (CLL). While producing durable responses and prolonging survival, roughly 20–25% of patients experience dose limiting side effects, mostly consisting of cardiovascular toxicities like severe hypertension and atrial fibrillation. While clinical predictors of BTK inhibitor-related cardiotoxicity have been proposed and may aid in risk stratification, there is no routine risk model used in clinical practice today to identify patients at highest risk. A recent study investigating genetic predictors of ibrutinib-related cardiotoxicity found that single nucleotide polymorphisms in KCNQ1 and GATA4 were significantly associated with cardiotoxic events. If replicated in larger studies, these biomarkers may improve risk stratification in combination with clinical factors. A clinicogenomic risk model may aid in identifying patients at highest risk of developing BTK inhibitor-related cardiotoxicity in which further risk mitigation strategies may be explored.


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