Genetic determinants of anthracycline cardiotoxicity – ready for the clinic?

Pharmacogenomic screening for anthracycline‐induced cardiotoxicity in childhood cancer

“…Functional studies of RARG rs2229774 have tied this variant to dysregulation of topoisomerase IIb, in line with the role of TOP2B in anthracycline-induced cardiotoxicity [3,6,7]. As pointed out by Craig et al [1] , UGT1A6 and SLC28A3 may not be expressed in the heart. However, the robustness of these associations suggests that they exert at least indirect effects on cardiac tissue, possibly through anthracycline biotransformation in other tissues.…”

“…Despite the robust pharmacogenomic associations that have been demonstrated as well as replicated, we agree that studies in additional cohorts, including patients of different ancestries, would be helpful in developing a more fulsome understanding of all the genomic predictors of anthracycline-induced cardiotoxicity and protection against this serious adverse drug reaction. As Craig et al [1] point out, anthracycline treatment remains one of the most important therapeutic options for a variety of paediatric cancers. We recognize, that for clinicians, the primary focus is the efficacy and cure rates in cancer patients.…”

“…As Craig et al . point out, anthracycline treatment remains one of the most important therapeutic options for a variety of paediatric cancers. We recognize, that for clinicians, the primary focus is the efficacy and cure rates in cancer patients.…”

“…We read with interest the comments from Craig et al . regarding our recently published clinical practice guidelines for pharmacogenomic testing in anthracycline‐based cancer treatment . Craig et al specifically posit that a functional and mechanistic understanding of pharmacogenomic associations is required prior to the issuance of clinical practice guidelines.…”

Systematic review of pharmacogenomics and adverse drug reactions in paediatric oncology patients

“…recommended genomic testing for retinoic acid receptor gamma rs2229774 (S427 L), SLC28A3 rs7853758 (L461 L) and UGT1A6 rs17863783 (V209 V). This was challenged by Craig et al . who raised the point that SLC28A3 rs7853758 and UGT1A6 rs17863783, in particular, require further validation since neither alter protein coding for these genes, and UGT1A6 rs17863783 is intronic in some alternate transcripts.…”