Momelotinib in myelofibrosis and beyond: a comprehensive review of therapeutic insights in hematologic malignancies

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 a...

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Bibliographic Details
Published in:Discover. Oncology 2024-08, Vol.15 (1), p.370-17
Main Authors: Dadkhah, Parisa alsadat, Karimi, Mohammad Amin, Chahkand, Mohammad Sadra Gholami, Moallem, Fatemeh Esmaeilpour, Kazemabad, Mohammad Javad Emami, Azarm, Eftekhar
Format: Article
Language:English
Subjects:
Anemia
Blood
Bone marrow
Cancer Research
Cytokines
Drug dosages
Hematologic diseases
Hemoglobin
Homeostasis
Internal Medicine
Iron
Kinases
Liver
Medicine
Medicine & Public Health
Molecular Medicine
Momelotinib
Myelofibrosis
Oncology
Pharmacokinetics
Proteins
Radiotherapy
Review
Splenomegaly
Surgical Oncology
Transfusion
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Summary: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. Highlights MF is a complex hematological malignancy that has the potential to transform into acute myeloid leukemia in 20 % of cases Anemia occurs in approximately one-third of MF patients Momelotinib is a novel ACVR1 antagonist and a dual inhibitor of the JAK1 and JAK2 enzymes just FDA approved on September 15 A comprehensive applied review of this novel agent is lacking
ISSN:2730-6011
2730-6011
DOI:10.1007/s12672-024-01252-1