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Sendino et al. Cancer Drug Resist 2018;1:139-63 Cancer
DOI: 10.20517/cdr.2018.09 Drug Resistance

Review Open Access

Hitting a moving target: inhibition of the nuclear
export receptor XPO1/CRM1 as a therapeutic
approach in cancer

Maria Sendino , Miren Josu Omaetxebarria , Jose Antonio Rodríguez 1
2
1
1 Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa
48940, Spain.
2 Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Leioa 48940, Spain.

Correspondence to: Dr. Jose Antonio Rodríguez. Department of Genetics, Physical Anthropology and Animal Physiology,
University of the Basque Country (UPV/EHU), Leioa 48940, Spain. E-mail: josean.rodriguez@ehu.es

How to cite this article: Sendino M, Omaetxebarria MJ, Rodríguez JA. Hitting a moving target: inhibition of the nuclear export
receptor XPO1/CRM1 as a therapeutic approach in cancer. Cancer Drug Resist 2018;1:139-63.
http://dx.doi.org/10.20517/cdr.2018.09

Received: 28 Jun 2018 First Decision: 24 Jul 2018 Revised: 3 Aug 2018 Accepted: 10 Aug 2018 Published: 19 Sep 2018
Science Editor: Godefridus J. Peters Copy Editor: Yuan-Li Wang Production Editor: Huan-Liang Wu

Abstract
Cellular homeostasis crucially relies on the correct nucleocytoplasmic distribution of a vast number of proteins and RNA
molecules, which are shuttled in and out of the nucleus by specialized transport receptors. The nuclear export receptor
XPO1, also called CRM1, mediates the translocation of hundreds of proteins and several classes of RNA to the cytoplasm,
and thus regulates critical signaling pathways and cellular functions. The normal function of XPO1 appears to be often
disrupted in malignant cells due to gene mutations or, most commonly, aberrant overexpression. Due to its important
physiological roles and its frequent alteration in human tumors, XPO1 is a promising target for cancer therapy. XPO1
inhibitors have undergone extensive testing as therapeutic agents in preclinical models of cancer, with promising results.
One of these inhibitors, Selinexor, is currently being evaluated in multiple clinical trials of different types of solid tumors
and hematological malignancies. Here, we review several key aspects of XPO1 function, as well as the mechanisms that
may lead to its alteration in cancer, and provide an update on the status of XPO1 inhibitors being developed as drugs for
cancer therapy, including the definitive results of the first clinical trials with Selinexor that have been recently published.

Keywords: XPO1, CRM1, nucleocytoplasmic transport, Selinexor

INTRODUCTION
In 1997, a 120 kDa protein called CRM1, known to function as a chromosome region maintenance fac-

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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