Nuclear transport inhibition in acute myeloid leukemia: recent advances and future perspectives

Selective inhibitors of nuclear export (SINE) are emerging as a potentially efficacious therapeutic strategy for overcoming resistance to conventional chemotherapy for acute myeloid leukemia. SINE specifically block the protein Exportin 1, also known as chromosomal region maintenance 1, leading to n...

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Bibliographic Details
Published in:International journal of hematologic oncology 2018-10, Vol.7 (3), p.IJH04-IJH04
Main Authors: Talati, Chetasi, Sweet, Kendra L
Format: Article
Language:English
Subjects:
acute myeloid leukemia
Apoptosis
Blood
Cell cycle
Chemotherapy
CRM1 inhibitor
Cytogenetics
Kinases
KPT-8602
Leukemia
Mutation
nuclear transport inhibitor
Patients
Proteins
Review
selinexor
Stem cells
XPO1 inhibitor
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Summary:Selective inhibitors of nuclear export (SINE) are emerging as a potentially efficacious therapeutic strategy for overcoming resistance to conventional chemotherapy for acute myeloid leukemia. SINE specifically block the protein Exportin 1, also known as chromosomal region maintenance 1, leading to nuclear retention of cargo proteins, including several tumor suppressor proteins. Selinexor, a first generation SINE, is currently in early phase clinical studies in various combinations with promising antileukemic and pro-apoptotic activity. Here we discuss the mechanism of action of SINEs and further elaborate on the clinical data available from the various trials in acute myeloid leukemia.
ISSN:2045-1393
2045-1407
DOI:10.2217/ijh-2018-0001