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

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.

• Authors: Muna Suleiman, Afnan Al Najjar, Zain Z Zakaria, Rashid Ahmed, Huseyin C Yalcin, Hesham M Korashy, Shahab Uddin, Sadaf Riaz, Nabeel Abdulrahman, Fatima Mraiche
• Journal: Journal of cardiovascular translational research (J Cardiovasc Transl Res) Vol. 17 Issue 2 Pg. 334-344 (04 2024) ISSN: 1937-5395 [Electronic] United States
• PMID: 37725271 (Publication Type: Journal Article, Review)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Ribosomal Protein S6 Kinases, 90-kDa
• Protein Kinase Inhibitors
• Antineoplastic Agents
• Tyrosine Kinase Inhibitors

Topics

• Humans
• Ribosomal Protein S6 Kinases, 90-kDa (metabolism, antagonists & inhibitors)
• Protein Kinase Inhibitors (adverse effects)
• Cardiotoxicity
• Animals
• Heart Diseases (chemically induced, enzymology, prevention & control)
• Signal Transduction (drug effects)
• Antineoplastic Agents (adverse effects)
• Neoplasms (drug therapy, enzymology)
• Tyrosine Kinase Inhibitors