Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors : Emphasis on ponatinib
Copyright © 2020 Elsevier B.V. All rights reserved..
The advent of tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. However, cardiotoxicity associated with these targeted therapies puts the cancer survivors at higher risk. Ponatinib is a third-generation TKI for the treatment of CML patients having gatekeeper mutation T315I, which is resistant to the first and second generation of TKIs, namely, imatinib, nilotinib, dasatinib, and bosutinib. Multiple unbiased screening from our lab and others have identified ponatinib as most cardiotoxic FDA approved TKI among the entire FDA approved TKI family (total 50+). Indeed, ponatinib is the only treatment option for CML patients with T315I mutation. This review focusses on the cardiovascular risks and mechanism/s associated with CML TKIs with a particular focus on ponatinib cardiotoxicity. We have summarized our recent findings with transgenic zebrafish line harboring BNP luciferase activity to demonstrate the cardiotoxic potential of ponatinib. Additionally, we will review the recent discoveries reported by our and other laboratories that ponatinib primarily exerts its cardiotoxicity via an off-target effect on cardiomyocyte prosurvival signaling pathways, AKT and ERK. Finally, we will shed light on future directions for minimizing the adverse sequelae associated with CML-TKIs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:316 |
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| Enthalten in: |
International journal of cardiology - 316(2020) vom: 01. Okt., Seite 214-221 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Singh, Anand Prakash [VerfasserIn] |
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| Links: |
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| Themen: |
4340891KFS |
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| Anmerkungen: |
Date Completed 14.05.2021 Date Revised 02.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijcard.2020.05.077 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310510562 |
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| 500 | |a Date Revised 02.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a The advent of tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. However, cardiotoxicity associated with these targeted therapies puts the cancer survivors at higher risk. Ponatinib is a third-generation TKI for the treatment of CML patients having gatekeeper mutation T315I, which is resistant to the first and second generation of TKIs, namely, imatinib, nilotinib, dasatinib, and bosutinib. Multiple unbiased screening from our lab and others have identified ponatinib as most cardiotoxic FDA approved TKI among the entire FDA approved TKI family (total 50+). Indeed, ponatinib is the only treatment option for CML patients with T315I mutation. This review focusses on the cardiovascular risks and mechanism/s associated with CML TKIs with a particular focus on ponatinib cardiotoxicity. We have summarized our recent findings with transgenic zebrafish line harboring BNP luciferase activity to demonstrate the cardiotoxic potential of ponatinib. Additionally, we will review the recent discoveries reported by our and other laboratories that ponatinib primarily exerts its cardiotoxicity via an off-target effect on cardiomyocyte prosurvival signaling pathways, AKT and ERK. Finally, we will shed light on future directions for minimizing the adverse sequelae associated with CML-TKIs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Cardio-oncology | |
| 650 | 4 | |a Cardiotoxicity | |
| 650 | 4 | |a Ponatinib | |
| 650 | 4 | |a Tyrosine kinase inhibitor | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Pyridazines |2 NLM | |
| 650 | 7 | |a ponatinib |2 NLM | |
| 650 | 7 | |a 4340891KFS |2 NLM | |
| 700 | 1 | |a Umbarkar, Prachi |e verfasserin |4 aut | |
| 700 | 1 | |a Tousif, Sultan |e verfasserin |4 aut | |
| 700 | 1 | |a Lal, Hind |e verfasserin |4 aut | |
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