Therapeutic targeting of exportin-1 in childhood cancer

Basia Galinski; Thomas B. Alexander; Daniel A. Mitchell; Hannah V. Chatwin; Chidiebere Awah; Adam L. Green; Daniel A. Weiser

doi:10.3390/cancers13246161

Therapeutic targeting of exportin-1 in childhood cancer

Basia Galinski, Thomas B. Alexander, Daniel A. Mitchell, Hannah V. Chatwin, Chidiebere Awah, Adam L. Green, Daniel A. Weiser

Pediatrics

Research output: Contribution to journal › Review article › peer-review

2 Scopus citations

Abstract

Overexpression of Exportin-1 (XPO1), a key regulator of nuclear-to-cytoplasmic transport, is associated with inferior patient outcomes across a range of adult malignancies. Targeting XPO1 with selinexor has demonstrated promising results in clinical trials, leading to FDA approval of its use for multiple relapsed/refractory cancers. However, XPO1 biology and selinexor sensitivity in childhood cancer is only recently being explored. In this review, we will focus on the differential biology of childhood and adult cancers as it relates to XPO1 and key cargo proteins. We will further explore the current state of pre-clinical and clinical development of XPO1 inhibitors in childhood cancers. Finally, we will outline potentially promising future therapeutic strategies for, as well as potential challenges to, integrating XPO1 inhibition to improve outcomes for children with cancer.

Original language	English (US)
Article number	6161
Journal	Cancers
Volume	13
Issue number	24
DOIs	https://doi.org/10.3390/cancers13246161
State	Published - Dec 1 2021

Keywords

Childhood cancer
Exportin-1
Nuclear export
SINE compounds
Selinexor

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers13246161

Cite this

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title = "Therapeutic targeting of exportin-1 in childhood cancer",

abstract = "Overexpression of Exportin-1 (XPO1), a key regulator of nuclear-to-cytoplasmic transport, is associated with inferior patient outcomes across a range of adult malignancies. Targeting XPO1 with selinexor has demonstrated promising results in clinical trials, leading to FDA approval of its use for multiple relapsed/refractory cancers. However, XPO1 biology and selinexor sensitivity in childhood cancer is only recently being explored. In this review, we will focus on the differential biology of childhood and adult cancers as it relates to XPO1 and key cargo proteins. We will further explore the current state of pre-clinical and clinical development of XPO1 inhibitors in childhood cancers. Finally, we will outline potentially promising future therapeutic strategies for, as well as potential challenges to, integrating XPO1 inhibition to improve outcomes for children with cancer.",

keywords = "Childhood cancer, Exportin-1, Nuclear export, SINE compounds, Selinexor",

author = "Basia Galinski and Alexander, {Thomas B.} and Mitchell, {Daniel A.} and Chatwin, {Hannah V.} and Chidiebere Awah and Green, {Adam L.} and Weiser, {Daniel A.}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = dec,

day = "1",

doi = "10.3390/cancers13246161",

language = "English (US)",

volume = "13",

journal = "Cancers",

issn = "2072-6694",

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T1 - Therapeutic targeting of exportin-1 in childhood cancer

AU - Galinski, Basia

AU - Alexander, Thomas B.

AU - Mitchell, Daniel A.

AU - Chatwin, Hannah V.

AU - Awah, Chidiebere

AU - Green, Adam L.

AU - Weiser, Daniel A.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Overexpression of Exportin-1 (XPO1), a key regulator of nuclear-to-cytoplasmic transport, is associated with inferior patient outcomes across a range of adult malignancies. Targeting XPO1 with selinexor has demonstrated promising results in clinical trials, leading to FDA approval of its use for multiple relapsed/refractory cancers. However, XPO1 biology and selinexor sensitivity in childhood cancer is only recently being explored. In this review, we will focus on the differential biology of childhood and adult cancers as it relates to XPO1 and key cargo proteins. We will further explore the current state of pre-clinical and clinical development of XPO1 inhibitors in childhood cancers. Finally, we will outline potentially promising future therapeutic strategies for, as well as potential challenges to, integrating XPO1 inhibition to improve outcomes for children with cancer.

AB - Overexpression of Exportin-1 (XPO1), a key regulator of nuclear-to-cytoplasmic transport, is associated with inferior patient outcomes across a range of adult malignancies. Targeting XPO1 with selinexor has demonstrated promising results in clinical trials, leading to FDA approval of its use for multiple relapsed/refractory cancers. However, XPO1 biology and selinexor sensitivity in childhood cancer is only recently being explored. In this review, we will focus on the differential biology of childhood and adult cancers as it relates to XPO1 and key cargo proteins. We will further explore the current state of pre-clinical and clinical development of XPO1 inhibitors in childhood cancers. Finally, we will outline potentially promising future therapeutic strategies for, as well as potential challenges to, integrating XPO1 inhibition to improve outcomes for children with cancer.

KW - Childhood cancer

KW - Exportin-1

KW - Nuclear export

KW - SINE compounds

KW - Selinexor

UR - http://www.scopus.com/inward/record.url?scp=85120656686&partnerID=8YFLogxK

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U2 - 10.3390/cancers13246161

DO - 10.3390/cancers13246161

M3 - Review article

AN - SCOPUS:85120656686

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 24

M1 - 6161

ER -

Therapeutic targeting of exportin-1 in childhood cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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