Genetic factors in anthracycline-induced cardiotoxicity in patients treated for pediatric cancer

ABSTRACT

Introduction

Cardiovascular diseases are the main cause of treatment-related morbidity and mortality in childhood cancer patients. Anthracyclines, one of the most common chemotherapeutic agents in treatment regimens, are implicated in chemotherapy-induced cardiotoxicity.

Areas covered

This review describes the pharmacogenomic markers related to anthracycline-induced cardiotoxicity affecting childhood cancer patients. We also included a brief overview of the applicability of reported findings to the well-established PETALE cohort of childhood acute lymphoblastic leukemia survivors of the Sainte-Justine University Health Center (Canada).

Expert opinion

The wide variation in interindividual susceptibility to anthracycline-induced cardiotoxicity, along with a multitude of genetic variants detected through association studies, suggests that genetic contributions could be essential for the design of new individualized preventive approaches.

KEYWORDS:

• Anthracycline-induced cardiotoxicity
• genetic association studies
• pharmacogenomic markers
• doxorubicin
• childhood cancer

Article highlights

• Anthracyclines, highly effective anticancer agents widely used to treat a variety of childhood malignancies, are linked to chemotherapy‐induced cardiotoxicity.

• Known clinical and treatment-related risk factors do not adequately explain variability in response to anthracyclines, suggesting the contribution of genetic determinants.

• Gene-treatment interactions in the context of specific treatment protocols are important for the implementation of pharmacogenetics findings.

This box summarizes the key points contained in the article.

Acknowledgments

The authors would like to thank all childhood ALL survivors and their parents for the participation in the PETALE study.

Supplementary material

Supplemental data for this article can be accessed here.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon request.

Ethics approval and consent to participate

Written informed consent was obtained from every patient or parent/legal guardian. The study was conducted in accordance with the Declaration of Helsinki and the protocol was approved by the Ethics Committee of SJUHC.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Institute of Cancer Research (ICR) of the Canadian Institutes of Health Research (CIHR) grant number: 118694, Cancer Research Society (CRS), Canadian Cancer Society Research Institute (CCSRI), Ontario Institute for Cancer Research (OICR), Pediatric Oncology Group of Ontario (POGO), Garron Family Cancer Centre at SickKids Hospital (Ontario), The Terry Fox foundation, FRQS Applied Medical Genetics Network and Sainte-Justine Hospital Foundation supported the PETALE study. K Petrykey is a scholar of the Cole Foundation.