Dadkhah Parisa Alsadat, Karimi Mohammad Amin, Chahkand Mohammad Sadra Gholami, Moallem Fatemeh Esmaeilpour, Kazemabad Mohammad Javad Emami, Azarm Eftekhar
School of Medicine, Isfahan University of Medical Sciences, Hezar Jerib Ave, Isfahan, Iran.
School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Discov Oncol. 2024 Aug 27;15(1):370. doi: 10.1007/s12672-024-01252-1.
Myelofibrosis (MF), a complex hematological malignancy, presents a diverse array of symptoms, including anemia, constitutional symptoms, bone marrow insufficiency, and splenomegaly. The latter, often necessitating blood transfusions, poses an essential obstacle to MF management. While conventional approaches predominantly involve the use of JAK inhibitors, the potential for exacerbating anemia introduces complexity to the treatment. Nonetheless, Momelotinib stands out as a promising pharmaceutical compound with the potential to revolutionize the field. Momelotinib is an ACVR1 antagonist and a dual inhibitor of the JAK1 and JAK2 enzymes. By targeting MF's hematological and fibrotic aspects, Momelotinib influences iron metabolism by regulating hepcidin. This results in reduced hepcidin expression and increased iron availability, ultimately leading to improved anemia and reduced dependency on blood transfusion. This study aims to provide a concise overview of the pathogenesis of MF and elucidate the mechanism of action of Momelotinib. Subsequently, our review offers a practical summary encompassing the effects of Momelotinib in monotherapy, combined comparative drug therapy, and its associated side effects. Additionally, we explore the application of Momelotinib in other cancer types and investigate predictors for treatment success. Furthermore, we examine the utilization of Momelotinib in patients with liver and kidney failure.
骨髓纤维化(MF)是一种复杂的血液系统恶性肿瘤,表现出多种症状,包括贫血、全身症状、骨髓功能不全和脾肿大。后者常常需要输血,这对MF的治疗构成了重大障碍。虽然传统方法主要涉及使用JAK抑制剂,但加重贫血的可能性给治疗带来了复杂性。尽管如此,莫洛替尼作为一种有前景的药物化合物,有可能彻底改变该领域。莫洛替尼是一种激活素受体1(ACVR1)拮抗剂,也是JAK1和JAK2酶的双重抑制剂。通过针对MF的血液学和纤维化方面,莫洛替尼通过调节铁调素影响铁代谢。这导致铁调素表达降低和铁利用率增加,最终改善贫血并减少对输血的依赖。本研究旨在简要概述MF的发病机制,并阐明莫洛替尼的作用机制。随后,我们的综述提供了一个实用的总结,涵盖了莫洛替尼在单药治疗、联合对比药物治疗中的效果及其相关副作用。此外,我们探讨了莫洛替尼在其他癌症类型中的应用,并研究治疗成功的预测因素。此外,我们还研究了莫洛替尼在肝肾功能衰竭患者中的应用。