Open AccessSTAT3 Inhibitors: Finding a Home in Lymphoma and Leukemia
Author(s) -
Munoz Javier,
Dhillon Navjot,
Janku Filip,
Watowich Stephanie S.,
Hong David S.
Publication year - 2014
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2013-0407
Subject(s) - janus kinase , cancer research , stat3 , pim1 , stat protein , jak stat signaling pathway , stat , stat4 , medicine , signal transduction , transcription factor , leukemia , immunology , tyrosine kinase , phosphorylation , cytokine , biology , microbiology and biotechnology , gene , genetics , serine
The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is an active mediator of cytokine signaling in the pathogenesis of solid and hematologic malignancies. The seven‐member STAT family is composed of latent cytoplasmic transcription factors that are activated by phosphorylation intertwined in a network with activation that ultimately leads to cell proliferation. An activated kinase enzyme phosphorylates one STAT factor or more, which shuttle to the nucleus to regulate gene expression, promoting cell survival. Somatic STAT3 mutations have been recently reported in large granular lymphocytic leukemia, aplastic anemia, and myelodysplastic syndrome. Furthermore, the relationship between BCL6 and STAT3 in diffuse large B‐cell lymphomas, particularly on the activated B‐cell subtype, needs to be further explored. The search for therapeutic STAT3 inhibitors that abrogate the JAK/STAT pathway is currently under way. Targeting the STAT pathway, which seems to be critical in tumorigenesis, is promising for multiple malignancies including lymphoma and leukemia. In this paper, we review mechanisms of action, failures, and successes of STAT3 inhibitors.