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.

Nuclear export inhibitor Selinexor targeting XPO1 enhances coronavirus replication

“…Selinexor is currently approved for treating selected hematological malignancies such as multiple myeloma and diffuse large B-cell lymphoma (11, 48). Multiple clinical trials are presently undergoing to use Selinexor as a monotherapy or in combination with other treatments against diverse types of malignancies (49, 50). A Phase 2 placebo-controlled trial of oral Selinexor in COVID-19 patients did not show significant differences in clinical outcomes (NCT04349098).…”