Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
National Center for Cancer Care and Research, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar.
J Cardiovasc Transl Res. 2024 Apr;17(2):334-344. doi: 10.1007/s12265-023-10431-4. Epub 2023 Sep 19.
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.
靶向治疗，如酪氨酸激酶抑制剂（TKIs），已被批准用于治疗各种癌症类型。然而，TKI 诱导的心脏毒性是其使用的限制因素。这一问题引发了对潜在的心脏保护技术的研究需求，这些技术将与 TKIs 联合使用。核糖体 S6-激酶（RSKs）是丝裂原激活蛋白激酶（MAPK）途径的下游效应物；特定的 RSK 同工型，如 RSK1 和 RSK2，在癌细胞中表达，在癌细胞中，它们增加肿瘤增殖。对这些同工型的选择性靶向将导致肿瘤抑制。此外，在心脏中表达的 RSKs 的激活导致心肌肥厚和心律失常；因此，抑制 RSKs 将导致心脏保护。这篇综述文章概述了 RSK 抑制剂的有用性，它们可以作为新型药物，在未来的研究中评估它们在减少癌症增殖以及保护心脏免受 TKI 诱导的心脏毒性方面的作用。
