Abstract:
:Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC). AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in several cancer models. In the present study, the in vitro and in vivo effects of AZD1480 were evaluated in HNSCC preclinical models to test the potential use of JAK kinase inhibition for HNSCC therapy. AZD1480 treatment decreased HNSCC proliferation in HNSCC cell lines with half maximal effective concentration (EC50) values ranging from 0.9 to 4 μM in conjunction with reduction of pSTAT3(Tyr705) expression. In vivo antitumor efficacy of AZD1480 was demonstrated in patient-derived xenograft (PDX) models derived from two independent HNSCC tumors. Oral administration of AZD1480 reduced tumor growth in conjunction with decreased pSTAT3(Tyr705) expression that was observed in both PDX models. These findings suggest that the JAK1/2 inhibitors abrogate STAT3 signaling and may be effective in HNSCC treatment approaches.
journal_name
Neoplasiajournal_title
Neoplasia (New York, N.Y.)authors
Sen M,Pollock NI,Black J,DeGrave KA,Wheeler S,Freilino ML,Joyce S,Lui VW,Zeng Y,Chiosea SI,Grandis JRdoi
10.1016/j.neo.2015.01.003subject
Has Abstractpub_date
2015-03-01 00:00:00pages
256-64issue
3eissn
1522-8002issn
1476-5586pii
S1476-5586(15)00014-7journal_volume
17pub_type
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