selinexor

Overview

Selinexor (KPT-330) is a selective inhibitor of nuclear export (SINE compound) that covalently binds XPO1 (exportin-1/CRM1), blocking nuclear export of tumor-suppressor proteins (p53, cyclin D1, c-Myc, PUMA, BIM). It is FDA-approved in relapsed/refractory multiple myeloma and DLBCL but is under investigation in solid tumors.

Evidence in the corpus

• Submicromolar KPT-330 (selinexor) treatment of ESCC cell lines induced significant apoptosis (cleaved PARP), inhibited proliferation, and altered XPO1 cargo proteins (p53, cyclin D1, c-Myc, PUMA, BIM); XPO1 carries a recurrent D624G missense mutation and is overexpressed (mRNA and protein) in ESCC tumors, where high expression correlates with larger tumor size (P = 0.016) PMID:24686850

Resistance mechanisms

Cancer types (linked)

• ESCC — XPO1 D624G mutation and overexpression; preclinical selinexor activity demonstrated in cell lines

Sources

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