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Editorial
. 2024 Mar;134(5):502-504.
doi: 10.1161/CIRCRESAHA.124.324164. Epub 2024 Feb 29.

Ponatinib-Induced Cardiomyocyte Toxicity: Dark Side of the Integrated Stress Response

Felix G Liang  1   2 , Javid Moslehi  3 , Richard N Kitsis  4   1   2   5
Affiliations
Editorial

Ponatinib-Induced Cardiomyocyte Toxicity: Dark Side of the Integrated Stress Response

Felix G Liang et al. Circ Res. 2024 Mar.
No abstract available

Keywords: Editorials; cardiomyopathies; integrated stress response; ponatinib.

PubMed Disclaimer

Conflict of interest statement

Disclosures J. Moslehi has provided consulting for Pfizer, Novartis, Bristol-Myers Squibb, Takeda, AstraZeneca, Regeneron, Daiichi Sankyo, BeiGene, Bitterroot Bio, and Cytokinetics.

Figures

Figure
Figure. Adaptive and maladaptive roles of the integrated stress response in cardiac pathophysiology.
See text for details. ATF4 activating transcription factor 4; eIF2α eukaryotic translation initiation factor 2 α-subunit; GCN2 general control nonderepressible-2; ISRIB integrated stress response inhibitor; P phosphorylation; PERK PKR-like ER kinase; PTM post-translational modifications. The biochemical function of ISRIB is to promote eIF2B assembly. This figure illustrates its functional effects on the ISR.
See this image and copyright information in PMC

Comment on

References

    1. Yan GHZ, Kwon Y, Jousma J, Nukala SB, Du X, Pinho S, Ong S-B, Lee WH, Ong S-G. Paradoxical activation of gcn2-mediated integrated stress response by ponatinib-induced mitochondrial dysfunction underlies its cardiotoxicity. Circ Res. 2024;134: xx–xxx. - PMC - PubMed
    1. Groarke JD, Cheng S, Moslehi J. Cancer-drug discovery and cardiovascular surveillance. N Engl J Med. 2013;369:1779–1781 - PubMed
    1. Singh AP, Glennon MS, Umbarkar P, Gupte M, Galindo CL, Zhang Q, Force T, Becker JR, Lal H. Ponatinib-induced cardiotoxicity: Delineating the signalling mechanisms and potential rescue strategies. Cardiovasc Res. 2019;115:966–977 - PMC - PubMed
    1. Tousif S, Singh AP, Umbarkar P, Galindo C, Wheeler N, Toro Cora A, Zhang Q, Prabhu SD, Lal H. Ponatinib drives cardiotoxicity by s100a8/a9-nlrp3-il-1beta mediated inflammation. Circ Res. 2023;132:267–289 - PMC - PubMed
    1. Costa-Mattioli M, Walter P. The integrated stress response: From mechanism to disease. Science. 2020;368 - PMC - PubMed