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The Role of p90 Ribosomal S6 Kinase (RSK) in Tyrosine Kinase Inhibitor (TKI)-Induced Cardiotoxicity

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Abstract

Targeted therapy, such as tyrosine kinase inhibitors (TKIs), has been approved to manage various cancer types. However, TKI-induced cardiotoxicity is a limiting factor for their use. This issue has raised the need for investigating potential cardioprotective techniques to be combined with TKIs. Ribosomal S6-kinases (RSKs) are a downstream effector of the mitogen-activated-protein-kinase (MAPK) pathway; specific RSK isoforms, such as RSK1 and RSK2, have been expressed in cancer cells, in which they increase tumour proliferation. Selective targeting of those isoforms would result in tumour suppression. Moreover, activation of RSKs expressed in the heart has resulted in cardiac hypertrophy and arrhythmia; thus, inhibiting RSKs would result in cardio-protection. This review article presents an overview of the usefulness of RSK inhibitors that can be novel agents to be assessed in future research for their effect in reducing cancer proliferation, as well as protecting the heart from cardiotoxicity induced by TKIs.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar

    Muna Suleiman

  2. National Center for Cancer Care and Research, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

    Afnan Al Najjar, Hesham M. Korashy & Fatima Mraiche

  3. Medical and Health Sciences, Qatar University, PO Box 2713, Doha, Qatar

    Zain Z. Zakaria

  4. Department of Biotechnology, Faculty of Science, Mirpur University of Science and Technology, Mirpur, 10250, AJK, Pakistan

    Rashid Ahmed

  5. Biomedical Research Centre (BRC), Qatar University, PO Box 2713, Doha, Qatar

    Huseyin C. Yalcin

  6. College of Health Sciences, QU-Health, Qatar University, PO Box 2713, Doha, Qatar

    Huseyin C. Yalcin & Nabeel Abdulrahman

  7. Translational Research Institute and Dermatology Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

    Shahab Uddin

  8. Pharmacy Department, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

    Sadaf Riaz

  9. Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

    Fatima Mraiche

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  1. Muna Suleiman
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Suleiman, M., Al Najjar, A., Zakaria, Z.Z. et al. The Role of p90 Ribosomal S6 Kinase (RSK) in Tyrosine Kinase Inhibitor (TKI)-Induced Cardiotoxicity. J. of Cardiovasc. Trans. Res. 17, 334–344 (2024). https://doi.org/10.1007/s12265-023-10431-4

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