Abstract
Cellular homeostasis requires the proper nuclear-cytoplasmic partitioning of large molecules, which is often deregulated in cancer. XPO1 is an export receptor responsible for the nuclear-cytoplasmic transport of hundreds of proteins and multiple RNA species. XPO1 is frequently overexpressed and/or mutated in human cancers and functions as an oncogenic driver. Suppression of XPO1-mediated nuclear export, therefore, presents a unique therapeutic strategy. In this review, we summarize the physiological functions of XPO1 as well as the development of various XPO1 inhibitors and provide an update on the recent clinical trials of the SINE compounds. We also discuss potential future research directions on the molecular function of XPO1 and the clinical application of XPO1 inhibitors.
Keywords:
CRM1; Cancer; Nuclear export; Selective inhibitor of nuclear export (SINE); Selinexor; XPO1.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Active Transport, Cell Nucleus / drug effects*
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Exportin 1 Protein
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Forecasting
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Gastrointestinal Diseases / chemically induced
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Hematologic Diseases / chemically induced
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Humans
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Hydrazines / adverse effects
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Hydrazines / therapeutic use
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Karyopherins / antagonists & inhibitors*
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Karyopherins / physiology
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Molecular Targeted Therapy*
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / metabolism
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RNA, Neoplasm / metabolism
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
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Receptors, Cytoplasmic and Nuclear / physiology
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Triazoles / adverse effects
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Triazoles / therapeutic use
Substances
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Antineoplastic Agents
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Hydrazines
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Karyopherins
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Neoplasm Proteins
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RNA, Neoplasm
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Receptors, Cytoplasmic and Nuclear
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Triazoles
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selinexor