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

Research output: Contribution to journalReview articlepeer-review

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 languageEnglish (US)
Article number6161
JournalCancers
Volume13
Issue number24
DOIs
StatePublished - Dec 1 2021

Keywords

  • Childhood cancer
  • Exportin-1
  • Nuclear export
  • SINE compounds
  • Selinexor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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