Authors
Y Chen, C Camacho, TR Silvers, AR Razak, JF Gabrail, NY, Gerecitano, E Kalir, E Pereira, BR Evans, SJ Ramus, F Huang, N Priedigkeit, E Rodriguez, M Donovan, FM Khan, T Kalir, RP Sebra, A Uzilov, R Chen, R Sinha, R Halpert, JN Billaud, S Shacham, D McCauley, Y Landesman, T Rashal, M Kauffman, MR Mirza, M Mau-Sørensen, P Dottino, JA Martignetti
Publication date
2017
Journal
Clin Cancer Res
Volume
23
Pages
1552-1563
Description
Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum-sensitive and -resistant ovarian cancer.
Experimental Design: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO datasets and tissue microarrays (TMA). The effect of XPO1 inhibition, using the small-molecule inhibitors KPT-185 and KPT-330 (selinexor) alone or in combination with a platinum agent on cell viability, apoptosis, and the transcriptome was tested in immortalized and patient-derived ovarian cancer cell lines (PDCL) and platinum-resistant mice (PDX). Seven patients with late …
Scholar articles
Y Chen, SC Camacho, TR Silvers, ARA Razak… - Clinical Cancer Research, 2017