Letter by Patanè Regarding Article, “Early Detection of Anthracycline Cardiotoxicity and Improvement With Heart Failure Therapy”

Abstract

1 with great interest and congratulate the authors for the completion of a burdensome work and the excellent presentation of their results. As the authors have correctly stated, early preclinical cardiac injury should be looked for soon after anthracycline treatment to effectively treat this disorder from its onset, before its overt clinical expression. However, I would like to point out one aspect that needs further clarification. The authors have reported that the overall incidence of cardiotoxicity is 9%. Previous researches have reported that anthracycline promotes cancer cell death via regulator of G-protein signaling 6 (RGS6)-mediated activation of ataxia telangiectasia-mutated serine/threonine protein kinase and the resultant upregulation of tumor suppressor p53, leading to an apoptosis pathway underlying its cytotoxic activity. The ability of RGS6 to promote p53 activation in response to anthracycline is independent of RGS6 interaction with G proteins but requires ataxia telangiectasia-mutated serine/threonine protein kinase and exhibits a reactive oxygen species-dependent, DNA damage-independent, and GGL and DEP domain-dependent mechanism.2-4 These results identify the GGL and DEP domains of RGS6 as essential mediators of the pathogenic responses to anthracycline in the heart, and they argue that the GGL and DEP domain inhibition of RGS6 offers a rational means to circumvent anthracycline cardiotoxicity in human patients with cancer 3 or that the presence of a GGL and DEP domain-altered mechanism could be a predictor of anthracycline-induced cardiotoxicity. I would like to observe that the authors have reported no relationships with RGS6, the GGL and DEP domains, ataxia telangiectasia-mutated serine/threonine protein kinase, p53, and reactive oxygen species. DisclosuresNone. Salvatore Patanè, MD