XPO1-dependent nuclear export as a target for cancer therapy

Nancy G Azizian, Yulin Li, Nancy G Azizian, Yulin Li

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.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
XPO1 mediates the nuclear export of hundreds of proteins and multiple RNA species

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