Ponatinib, But Not the New Abl-Kinase Inhibitor Asciminib, Activates Platelets, Leukocytes, and Endothelial Cell TNF Signaling to Induce Atherosclerotic Plaque Inflammation, Myocardial Infarction, and Stroke
Ponatinib, a potent anticancer therapy, activates ECs, platelets, and leukocytes, driving plaque inflammation and death from MI and stroke in mice, mirroring clinical cardiotoxicities in patients with cancer. Asciminib did not induce these effects, suggesting it might be a safer option for imatinib-resistant patients with cancer. Inhibition of TNFR-mediated endothelial activation is sufficient to prevent ponatinib-induced major adverse cardiovascular events.
Authors
- Richard J. Travers (ORCID: https://orcid.org/0000-0002-6839-4996)
- Sohel Shamsuzzaman (ORCID: https://orcid.org/0000-0003-2033-8976)
- Iris Z. Jaffe (ORCID: https://orcid.org/0000-0001-9300-1253)
- Rebecca A. Deaton (ORCID: https://orcid.org/0000-0001-7569-1924)
- Alec Stepanian (ORCID: https://orcid.org/0000-0003-4719-5792)
- Joshua J. Man (ORCID: https://orcid.org/0000-0002-2562-5715)
- Gary K. Owens (ORCID: https://orcid.org/0000-0002-7119-9657)
- Nicole L. Wolter (ORCID: https://orcid.org/0000-0001-9805-1380)
- Christopher S. Chen (ORCID: https://orcid.org/0000-0003-2445-8449)
- Qing Lu (ORCID: https://orcid.org/0000-0003-2380-5330)
- Angelina Tesfu
Institutions
- Boston University (US)
- Tufts University (US)
- Tufts Medical Center (US)
- Inspire Institute (US)
- University of Virginia (US)
Publication Details
- Journal
- Circulation
- Published
- 2025-08-05
- DOI
- https://doi.org/10.1161/circulationaha.125.073610
- Citations
- 3
- Primary Topic
- Chronic Myeloid Leukemia Treatments
- Type
- article
- Field-Weighted Citation Impact
- 5.31