Novel Therapies in Myeloproliferative Neoplasms (MPN): Beyond JAK Inhibitors.

Abstract

PURPOSE OF REVIEW:

With increased understanding of the pathobiology of myeloproliferative neoplasms (MPNs), multiple new agents are now being investigated. We aim to cover some of the current treatment options for MPNs and discuss new agents in development.

RECENT FINDINGS:

The introduction of ruxolitinib improved the treatment of many patients with intermediate and higher risk myelofibrosis. However, ruxolitinib monotherapy does not benefit all patients, and not all patients can receive this therapy due to limiting cytopenias. The unraveling of new molecular abnormalities and cellular pathways led to the development of several novel targeted agents that are currently under investigation in clinical trials. These agents have different mechanisms of action and are being used either alone or in combination with ruxolitinib. Novel targets include inhibition of apoptosis, the tumor microenvironment, telomerase enzyme action, immunotherapy, and fibrosis with associated cytokines. We comprehensively review and summarize the available preclinical and clinical trials with novel agents for MPNs.

• Authors: Minas P Economides, Srdan Verstovsek, Naveen Pemmaraju
• Journal: Current hematologic malignancy reports (Curr Hematol Malig Rep) Vol. 14 Issue 5 Pg. 460-468 (10 2019) ISSN: 1558-822X [Electronic] United States
• PMID: 31372878 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Cytokines
• Janus Kinase Inhibitors
• Protein Kinase Inhibitors
• TP53 protein, human
• Tumor Suppressor Protein p53
• Janus Kinases

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Apoptosis (drug effects)
• Cytokines (metabolism)
• Hematopoietic Stem Cells (drug effects, metabolism)
• Humans
• Janus Kinase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Janus Kinases (antagonists & inhibitors)
• Molecular Targeted Therapy (methods)
• Myeloproliferative Disorders (diagnosis, drug therapy, etiology, metabolism)
• Protein Kinase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Signal Transduction (drug effects)
• Treatment Outcome
• Tumor Microenvironment (drug effects)
• Tumor Suppressor Protein p53 (genetics, metabolism)