Direct Targeting Options for STAT3 and STAT5 in Cancer.
STAT3
STAT5
cancer
small-molecule inhibitors
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
03 Dec 2019
03 Dec 2019
Historique:
received:
17
10
2019
revised:
22
11
2019
accepted:
29
11
2019
entrez:
11
12
2019
pubmed:
11
12
2019
medline:
11
12
2019
Statut:
epublish
Résumé
Signal transducer and activator of transcription (STAT)3 and STAT5 are important transcription factors that are able to mediate or even drive cancer progression through hyperactivation or gain-of-function mutations. Mutated STAT3 is mainly associated with large granular lymphocytic T-cell leukemia, whereas mutated STAT5B is associated with T-cell prolymphocytic leukemia, T-cell acute lymphoblastic leukemia and γδ T-cell-derived lymphomas. Hyperactive STAT3 and STAT5 are also implicated in various hematopoietic and solid malignancies, such as chronic and acute myeloid leukemia, melanoma or prostate cancer. Classical understanding of STAT functions is linked to their phosphorylated parallel dimer conformation, in which they induce gene transcription. However, the functions of STAT proteins are not limited to their phosphorylated dimerization form. In this review, we discuss the functions and the roles of unphosphorylated STAT3/5 in the context of chromatin remodeling, as well as the impact of STAT5 oligomerization on differential gene expression in hematopoietic neoplasms. The central involvement of STAT3/5 in cancer has made these molecules attractive targets for small-molecule drug development, but currently there are no direct STAT3/5 inhibitors of clinical grade available. We summarize the development of inhibitors against the SH2 domains of STAT3/5 and discuss their applicability as cancer therapeutics.
Identifiants
pubmed: 31817042
pii: cancers11121930
doi: 10.3390/cancers11121930
pmc: PMC6966570
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : Austrian Science Fund FWF
ID : I 4157
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : I 4218
Pays : Austria
Organisme : CIHR
ID : MOP-130424; MOP-137036
Pays : Canada
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