Correction: An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity

There was a mistake in figure legend for Figure 1 as published. We omitted the permission information for the figure in the figure legend. The corrected figure legend for Figure 1 appears below. FIGURE 1 Stages in the course of Anthracycline-induced ventricular dysfunction. (1) Primary prevention is possible at this stage by reducing risk factors in high-risk populations (such as those receiving anticancer therapy). (2) Secondary prevention is possible at this stage to reduce the effects of the treatment-induced injury. (3) Secondary prevention is also possible at this stage. (4) Clinically significant conduction and rhythm abnormalities might be observed. (5) Radical therapies might be required at this stage (such as heart transplant) if there is failure of medical management. Preventive strategies are progressively less effective as the toxicity increases. Treatment strategies have a greater impact when used to treat themore-diseased heart, but have longer effects if initiated early. Reproduced with permission from " Early Diagnosis and Prediction of Anticancer Drug-induced Cardiotoxicity: From Cardiac Imaging to "Omics" Technologies" by Rosalinda Madonna, purchased and obtained a licence from Elsevier. There was a mistake in figure legend for Figure 2 as published. We omitted the permission information for the figure in the figure legend. The corrected figure legend for Figure 2 appears below. FIGURE 2 Mechanisms of action of doxorubicin (DOX). DOX intercalates between strands of DNA double helix. The formation of a ternary complex (TOP2-DOX-DNA) prevents enzyme turnover. The latter blocks the catalytic cycle after DNA is cleaved and before DNA relegation. DOX biotransformation results in the formation of ROS. Reproduced with permission from "Update on pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity" by Raphaëlle Corremans, Rui Adão, Gilles W De Keulenaer, Adelino F Leite-Moreira and Carmen Brás-Silva, licensed under CC BY. There was a mistake in figure legend for Figure 3 as published. We omitted the permission information for the figure in the figure legend. The corrected figure legend for Figure 3 appears below. FIGURE 3 Doxorubicin (DOX) undergoes redoxcycling catalysed by NADPH-Cytochrome P-450 reductase. (A) The One-electron (1e-) reduction of the quinone compound leads to redox cycling and generation of superoxide anion radical. (B) O2-undergoes dismutation to form H2O2 either spontaneously or catalysed by superoxide dismutase. (C) H2O2 then reacts with the transition metal ion Fe2+, giving rise to -OH. Free Fe2+ is toxic to cells as catalyst in the formation of free radicals from ROS via the Fenton reaction. Last Name author1 et al. Frontiers Media SA 2 Reproduced with permission from "Update on pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity" by Raphaëlle Corremans, Rui Adão, Gilles W De Keulenaer, Adelino F Leite-Moreira and Carmen Brás-Silva, licensed under CC BY. The original version of this article has been updated. There was a mistake in figure legend for Figure 4 as published. We omitted the permission information for the figure in the figure legend. The corrected figure legend for Figure 4 appears below. FIGURE 4 Anthracycline drugs induced changes in mitochondrial membrane permeability and induced cell death. (A) Mitochondrial permeability transition pore (MPTP) structure. It was recently proposed that the MPTP is generally considered to be a complex channel composed of several proteins, including voltage-dependent anion channel 1 (VDAC1) in the outer membrane, adenine nucleotide translocase 1 (ANT1) in the inner membrane, and cyclophilin D (CYPD) in the mitochondrial matrix. In addition, the MPTP can be regulated by other components, such as hexokinase (HK), creatine kinase (CK), and peripheral-type benzodiazepine receptors (PBR). Both antiapoptotic and proapoptotic members of the Bcl-2 family modulate the activity of MPTP (antiapoptotic members of the Bcl-2 family, including Bcl-2 and Bcl-XL, inhibit pore openingwhile proapoptotic Bcl-2 family members, such as Bax, Bak, and Bid, can induce MPT pore opening). Also, MPT pore opening can be inhibited by CypD ligands, such as cyclosporin A (CsA). The opening of MPTP leads to a collapse of transmembrane mitochondrial transmembrane potential and favors the release of apoptogenic proteins, such as cytochrome c (Cyt c). (B) A large component of DOX induced cardiotoxicity is mediated by a redox cycle on mitochondrial complex I. Increased ROS generation by DOX redox cycle has several negative consequences, such as mitochondrial transmembrane potential disruption, MPTP formation, ATP depletion, and peroxidation of cellular membranes. Marked mitochondrial morphological disturbances induced by DOX include cristae disruption, matrix disorganization, and mitochondrial fragmentation. MPTP -induced outer membrane rupture due to osmotic swelling or permeabilization of the mitochondrial outer membrane mediated by proapoptotic proteins including BAX can lead to the release of cyt c and AIF. DOX also interferes with topoisomerase II, inhibiting DNA replication and preventing the repair of damage DNA strands. Finally, persistent downregulation of gene expression can be another consequence of DOX toxicity. All of these events may lead to cell death. Reproduced with permission from "Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy" by Filipa S Carvalho, Ana Burgeiro, Rita Garcia, António J Moreno, Rui A Carvalho and Paulo J Oliveira, licensed under CC BY. The original version of this article has been updated. There was a mistake in figure legend for Figure 5 as published. We omitted the permission information for the figure in the figure legend. The corrected figure legend for Figure 5 appears below. FIGURE 5 Anthracycline drugs can cause mitochondrial dysfunction by inhibiting the activity of mitochondrial transcription enzymes. These transcription enzymes mainly include Top1mt and mitochondrial transcription factors, and mitochondrial transcription factors include peroxisome proliferator-activated receptor-gamma coactivator-1α and 1β, Nuclear respiratory factor-1, mitochondrial transcription factor A (TFAM), and Tumor suppressor protein 53. Reproduced with permission from "Mitochondria and Doxorubicin-Induced Cardiomyopathy: A Complex Interplay" by Leonardo Schirone, Luca D'Ambrosio, Maurizio Forte, Riccardo Genovese, Sonia Schiavon, Giulia Spinosa, Giuliano Iacovone, Valentina Valenti, Giacomo Frati and Sebastiano Sciarretta, licensed under CC BY. The original version of this article has been updated. There was a mistake in figure legend for Figure 6 as published. We omitted the permission information for the figure in the figure legend. The corrected figure legend for Figure 6 appears below. FIGURE 6 Anthracycline-induced cell apoptosis is mitochondria-mediated intrinsic signaling. When anthracycline drugs enter cardiac myocytes, they cause the release of Cyt c from the mitochondrial inner membrane, which then binds to Apaf-1 to form the apoptosome. The apoptosome activates the caspase family, leading to cell apoptosis. AKT, as a key factor in the apoptosis signaling pathway, can inhibit cell apoptosis by regulating the Bcl-2 family. In addition to the mitochondria-mediated intrinsic signaling pathway, anthracycline drugs can also induce programmed necrosis and cell pyroptosis, resulting in damage to cardiac myocytes. Reproduced with permission from "An update of the molecular mechanisms underlying doxorubicin plus trastuzumab induced cardiotoxicity" by Miguel Anjos, Marta Fontes-Oliveira, Vera M Costa, Mário Santos and Rita Ferreira, licensed under CC BY. The original version of this article has been updated. There was a mistake in figure legend for Figure 7 as published. We omitted the permission information for the figure in the figure legend. The corrected figure legend for Figure 7 appears below. FIGURE 7 Contributors to Anthracycline -induced cardiovascular toxicity. A combination of clinical and genetic risk factors leads to increased risk of developing toxicity upon cancer therapy treatment. Elucidation of genetic contributors of cancer therapy-induced cardiovascular toxicity facilitates understanding of its molecular mechanism and development of its therapeutic strategies. Reproduced with permission from "Genetics of cancer therapy-associated cardiotoxicity" by Yuri Kim, Jonathan G Seidman and Christine E Seidman, licensed under CC BY. The original version of this article has been updated.