tofacitinib and Neoplasm-Metastasis

tofacitinib has been researched along with Neoplasm-Metastasis* in 1 studies

Other Studies

1 other study(ies) available for tofacitinib and Neoplasm-Metastasis

ArticleYear
JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma.
    Leukemia, 2014, Volume: 28, Issue:2

    Extranodal, nasal-type natural killer (NK)/T-cell lymphoma (NKCL) is an aggressive malignancy with poor prognosis in which, usually, signal transducer and activator of transcription 3 (STAT3) is constitutively activated and oncogenic. Here, we demonstrate that STAT3 activation mostly results from constitutive Janus kinase (JAK)3 phosphorylation on tyrosine 980, as observed in three of the four tested NKCL cell lines and in 20 of the 23 NKCL tumor samples under study. In one of the cell lines and in 4 of 19 (21%) NKCL primary tumor samples, constitutive JAK3 activation was related to an acquired mutation (A573V or V722I) in the JAK3 pseudokinase domain. We then show that constitutive activation of the JAK3/STAT3 pathway has a major role in NKCL cell growth and survival and in the invasive phenotype. Indeed, NKCL cell growth was slowed down in vitro by targeting JAK3 with chemical inhibitors or small-interfering RNAs. In a human NKCL xenograft mouse model, tumor growth was significantly delayed by the JAK3 inhibitor CP-690550. Altogether, the constitutive activation of JAK3, which can result from JAK3-activating mutations, is a frequent feature of NKCL that deserves to be tested as a therapeutic target.

    Topics: Adult; Aged; Aged, 80 and over; Animals; Case-Control Studies; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Models, Animal; Female; Gene Expression Regulation, Neoplastic; Humans; Janus Kinase 3; Lymphoma, Extranodal NK-T-Cell; Male; Mice; Middle Aged; Mutation; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Phosphorylation; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Tumor Burden; Xenograft Model Antitumor Assays

2014