TY - JOUR
T1 - Janus kinase inhibitors
T2 - An update on the progress and promise of targeted therapy in the myeloproliferative neoplasms
AU - Stein, Brady L.
AU - Crispino, John D.
AU - Moliterno, Alison R.
PY - 2011/11
Y1 - 2011/11
N2 - Purpose of Review: The discovery of the JAK2 V617F mutation in the classical myeloproliferative neoplasms (MPNs) essential thrombocytosis, polycythemia vera, and primary myelofibrosis has ushered in a new era of scientific discovery in these diseases, resulting in a molecular classification and an improved understanding of disease pathogenesis. Alongside this period of discovery has been the rapid development of targeted therapy and, here, we summarize results from clinical trials involving these small molecule Janus family of tyrosine kinase (JAK) inhibitors. Recent Findings: The JAK inhibitors consistently alleviate constitutional symptoms and reduce spleen size. Early phase testing indicates that some of these inhibitors have additional unique effects: INCB018424 results in a significant reduction in the level of pro-inflammatory cytokines; TG101348 may modify disease burden as assessed by JAK2 allele measurements; and CYT387 ameliorates anemia. Summary: The initial enthusiasm for these agents has been tempered by recognition that JAK2 V617F may represent only one component of lesions driving the heterogeneity of the MPN. Clinical trial design cannot address important disease endpoints such as thrombosis or leukemia transformation, but it appears that JAK inhibitors will offer an important palliative option and because of the molecular complexity in these diseases, it might be rational to give these inhibitors along with other agents that target alternate mechanisms of the disease pathogenesis.
AB - Purpose of Review: The discovery of the JAK2 V617F mutation in the classical myeloproliferative neoplasms (MPNs) essential thrombocytosis, polycythemia vera, and primary myelofibrosis has ushered in a new era of scientific discovery in these diseases, resulting in a molecular classification and an improved understanding of disease pathogenesis. Alongside this period of discovery has been the rapid development of targeted therapy and, here, we summarize results from clinical trials involving these small molecule Janus family of tyrosine kinase (JAK) inhibitors. Recent Findings: The JAK inhibitors consistently alleviate constitutional symptoms and reduce spleen size. Early phase testing indicates that some of these inhibitors have additional unique effects: INCB018424 results in a significant reduction in the level of pro-inflammatory cytokines; TG101348 may modify disease burden as assessed by JAK2 allele measurements; and CYT387 ameliorates anemia. Summary: The initial enthusiasm for these agents has been tempered by recognition that JAK2 V617F may represent only one component of lesions driving the heterogeneity of the MPN. Clinical trial design cannot address important disease endpoints such as thrombosis or leukemia transformation, but it appears that JAK inhibitors will offer an important palliative option and because of the molecular complexity in these diseases, it might be rational to give these inhibitors along with other agents that target alternate mechanisms of the disease pathogenesis.
KW - Janus family of tyrosine kinase inhibitors
KW - myeloproliferative neoplasms
KW - targeted therapies
UR - http://www.scopus.com/inward/record.url?scp=80054106619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054106619&partnerID=8YFLogxK
U2 - 10.1097/CCO.0b013e32834d1b22
DO - 10.1097/CCO.0b013e32834d1b22
M3 - Review article
C2 - 21993415
AN - SCOPUS:80054106619
SN - 1040-8746
VL - 23
SP - 609
EP - 616
JO - Current opinion in oncology
JF - Current opinion in oncology
IS - 6
ER -