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vestigations are required to address several salient questions on the use of XPO1 inhibition as a therapeutic
approach.
On one hand, novel XPO1 inhibitors with more favorable clinical properties are being developed. In this
regard, a “second-generation” SINE (KPT-8602 or Eltanexor) has demonstrated improved tolerability in
preclinical models [203-205] and is currently undergoing clinical evaluation.
On the other hand, it is necessary to further elucidate the mechanisms that mediate the oncogenic role of
XPO1 alterations (overexpression or mutation) in different types of cancer and to better characterize the
molecular and cellular mechanisms underlying the effect of XPO1 inhibitors. This basic mechanistic infor-
mation, which is still rather limited, would be crucial to successfully implement XPO1-targeting drugs in
the clinic, as it could help to design rational combinations with other agents, to identify subsets of patients
that may benefit more from the treatment and to improve the clinical management of adverse effects.
DECLARATIONS
Acknowledgments
We thank our colleagues at the UPV/EHU Dr. Sonia Bañuelos (Dept. of Biochemistry and Molecular Biol-
ogy), Dr. Gorka Prieto (Dept. of Communication Engineering) and Dr. Asier Fullaondo (Dept. of Genetics,
Physical Anthropology and Animal Physiology) for their help in preparing Figures 2 and 3. Supported by
grants from the Spanish Government MINECO-FEDER (SAF2014-57743-R), the Basque Country Govern-
ment (IT634-13) and the University of the Basque Country (UFI11/20), as well as a fellowship from the
Basque Country Government (to MS).
Authors’ contributions
Conception of the work, draft and revision of the work: Sendino M, OmaetxebarriaMJ, RodríguezJA
Availability of data and materials
Not applicable.
Financial support and sponsorship
None.
Conflicts of interest
All authors declared that there are no conflicts of interest.
Ethical approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Copyright
© The Author(s) 2018.
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