The future of JAK inhibition in myelofibrosis and beyond
The future of JAK inhibition in myelofibrosis and beyond
The identification of aberrant JAK–STAT signaling in patients with myeloproliferative neoplasms has served as the basis for the development of a new class of targeted agents. Ruxolitinib, the first-in-class oral small molecule JAK1/2 inhibitor, has demonstrated clinical efficacy and shown a potential overall survival benefit in two randomized phase III clinical trials. However, this agent has not been associated with improvements in cytopenias, molecular remissions, or resolution of bone marrow fibrosis. Therefore, further translational research is needed to improve the understanding of the pathogenetic mechanisms driving this myeloid malignancy to ultimately address remaining unmet clinical needs. A number of novel JAK inhibitors are being evaluated in ongoing clinical trials and the full clinical potential of these newer agents remains incompletely understood. The use of JAK inhibition in combination therapy approaches, as well as mono- and combination therapies in the treatment of advanced forms of polycythemia vera are also under active investigation. This review will update the reader on the current understanding of oncogenic JAK–STAT pathway activity in the pathogenesis of myeloproliferative neoplasms and the current success and limitations of anti-JAK therapy.
myeloproliferative neoplasms, myelofibrosis, plycythemia vera, jak, ruxolitnib
189-196
Mascarenhas, John O.
24678e3b-3c8c-479a-ac75-197dacc45b8c
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Mesa, Ruben A.
2199cfc1-60bf-4329-9293-3f0600dbcff3
September 2014
Mascarenhas, John O.
24678e3b-3c8c-479a-ac75-197dacc45b8c
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Mesa, Ruben A.
2199cfc1-60bf-4329-9293-3f0600dbcff3
Abstract
The identification of aberrant JAK–STAT signaling in patients with myeloproliferative neoplasms has served as the basis for the development of a new class of targeted agents. Ruxolitinib, the first-in-class oral small molecule JAK1/2 inhibitor, has demonstrated clinical efficacy and shown a potential overall survival benefit in two randomized phase III clinical trials. However, this agent has not been associated with improvements in cytopenias, molecular remissions, or resolution of bone marrow fibrosis. Therefore, further translational research is needed to improve the understanding of the pathogenetic mechanisms driving this myeloid malignancy to ultimately address remaining unmet clinical needs. A number of novel JAK inhibitors are being evaluated in ongoing clinical trials and the full clinical potential of these newer agents remains incompletely understood. The use of JAK inhibition in combination therapy approaches, as well as mono- and combination therapies in the treatment of advanced forms of polycythemia vera are also under active investigation. This review will update the reader on the current understanding of oncogenic JAK–STAT pathway activity in the pathogenesis of myeloproliferative neoplasms and the current success and limitations of anti-JAK therapy.
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More information
e-pub ahead of print date: 28 June 2014
Published date: September 2014
Keywords:
myeloproliferative neoplasms, myelofibrosis, plycythemia vera, jak, ruxolitnib
Organisations:
Human Development & Health
Identifiers
Local EPrints ID: 367225
URI: http://eprints.soton.ac.uk/id/eprint/367225
ISSN: 0268-960X
PURE UUID: c0c6af68-ca31-4753-bce5-6deb9be83483
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Date deposited: 19 Aug 2014 09:38
Last modified: 15 Mar 2024 03:11
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Author:
John O. Mascarenhas
Author:
Ruben A. Mesa
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