New study identifies association between ROBO2 and anthracycline-related cardiomyopathy in childhood cancer survivors

The study has important implications as anthracyclines are a widely used chemotherapy drug class to treat various forms of cancer, with 50-60 per cent of children with cancer being treated with anthracycline, says GlobalData

A genome-wide association study (GWAS) published in the Journal of Clinical Oncology has identified a potential association between a genetic variant, ROBO2, and anthracycline-related cardiomyopathy in childhood cancer survivors. The study has important implications as anthracyclines are a widely used chemotherapy drug class to treat various forms of cancer, with 50-60 per cent of children with cancer being treated with anthracycline, says GlobalData.

Continuous exposure to anthracyclines can lead to cardiac dysfunction, eventually resulting in cardiomyopathy. Cardiomyopathy is a term for a heterogenous collection of diseases that are characterised by impaired heart muscle, inhibiting the heart’s ability to pump blood throughout the body. Prevalent subtypes of cardiomyopathy include hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, and restrictive cardiomyopathy. These subtypes vary in clinical manifestation, from enlarged ventricles to thickened walls of the heart, and more. In time, the heart weakens, which can lead to heart failure.

Wang and colleagues examined 1,866 anthracycline-exposed Childhood Cancer Survivor Study participants to identify single-nucleotide polymorphisms (SNPs) with a statistically significant main or gene-environment interaction effect on anthracycline-related cardiomyopathy. Their findings led the researchers to conclude that SNP ROBO2 and high-dose anthracyclines promote cardiac fibrosis, which supports the plausibility of the association between ROBO2 and anthracycline-related cardiomyopathy.

Sarah Bundra, Analyst at GlobalData comments, “Cardiomyopathies can either be inherited genetically or acquired as a result of behaviors or other conditions. Wang and colleagues’ findings support an additional subtype of cardiomyopathy’s linkage to genetic variance.”

ROBO2 encodes transmembrane Robo receptors that bind Slit ligands. The researchers at the University of Alabama assert that Slit-Robo signaling pathways promote cardiac fibrosis by interfering with a pathway that thus results in disordered remodeling of the extracellular matrix and potentiating heart failure.

Bundra concludes, “These results hold important implications given the high number of child cancer patients treated with anthracyclines.”