Targeting nuclear import and export in hematological malignancies.
Active Transport, Cell Nucleus
/ drug effects
Animals
Antineoplastic Agents
/ pharmacology
Biomarkers, Tumor
Cell Transformation, Neoplastic
/ drug effects
Clinical Trials as Topic
Drug Development
Gene Expression Regulation, Neoplastic
/ drug effects
Hematologic Neoplasms
/ drug therapy
Humans
Karyopherins
/ antagonists & inhibitors
Molecular Targeted Therapy
Signal Transduction
/ drug effects
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
07
05
2020
accepted:
26
06
2020
revised:
25
06
2020
pubmed:
7
7
2020
medline:
1
12
2020
entrez:
7
7
2020
Statut:
ppublish
Résumé
The transport of proteins across the nuclear membrane is a highly regulated process, essential for the cell function. This transport is actively mediated by members of the karyopherin family, termed importins, or exportins, depending on the direction of transport. These proteins play an active part in tumorigenesis, through aberrant localization of their cargoes, which include oncogenes, tumor-suppressor genes and mediators of key signal transduction pathways. Overexpression of importins and exportins is reported in many malignancies, with implications in cell growth and viability, differentiation, drug resistance, and tumor microenvironment. Given their broad significance across tumors and pathways, much effort is being put to develop specific inhibitors as a novel anticancer therapeutics. Already, selinexor, a specific inhibitor of exportin-1 (XPO1), is approved for clinical use. This review will focus on the role of importins and exportins in hematological malignancies. We will discuss current preclinical and clinical data on importins and exportins, and demonstrate how our growing understanding of their functions has identified new therapeutic targets.
Identifiants
pubmed: 32624581
doi: 10.1038/s41375-020-0958-y
pii: 10.1038/s41375-020-0958-y
pmc: PMC7584478
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
Karyopherins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2875-2886Références
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