title: Targeting the JAK-STAT pathway in lymphoma: a focus on pacritinib.
abstract: BACKGROUND
  The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway mediates signaling by cytokine, chemokine and growth factor receptors on cell surface to the nucleus. JAK/STAT pathway is aberrantly activated in a variety of lymphomas, with a dual role of promoting cell survival/proliferation and immune evasion.
  
  
  METHODS
  This review describes the preclinical rationale behind the development of JAK inhibitors in lymphoma, some of which are being evaluated in Phase I/II studies, and summarizes the characteristics and clinical results of different JAK inhibitors in clinical development. Available preclinical and clinical data about JAK inhibition in lymphoid malignancies were reviewed using a PubMed access. To date, pacritinib (SB1518), a selective JAK2/FLT3 inhibitor is the first and only JAK inhibitor that has been evaluated in patients with relapsed lymphoma.
  
  
  CONCLUSIONS
  The preclinical rationale behind the development of pacritinib in lymphoproliferative neoplasms is strong, as the deregulation of the JAK/STAT pathway is involved in the pathogenesis of multiple lymphoma subtypes, although with different mechanisms. Pacritinib demonstrated safety and early clinical efficacy in a variety of lymphoma histologic types, providing the first proof of principle of the potential clinical value of targeting JAK/STAT pathway in lymphoma.
authors: University of Bologna, Institute of Hematology and Medical Oncology L.A. Seragnoli, Via Massarenti 9, 40138 Bologna, Italy. ederenzini@gmail.com
authors: Enrico
authors: E
authors: Derenzini
authors: Anas
authors: A
authors: Younes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000009:adverse effects / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology*; D050791:STAT Transcription Factors / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors
chemical_list: C561234:11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D050791:STAT Transcription Factors; D051941:fms-Like Tyrosine Kinase 3; D053614:Janus Kinase 2