Validation of a non-oncogene encoded vulnerability to Exportin 1 inhibition in pediatric renal tumors. Validation of a non-oncogene encoded vulnerability to Exportin 1 inhibition in pediatric renal tumors

We identified XPO1 as an aberrantly activated, non-oncogene encoded targetable vulnerability in pediatric renal tumors (Wilms and malignant rhabdoid tumor [MRT]) using OncoTarget, a Master Regular-based precision cancer medicine tool. We demonstrate significant anti-tumor activity of selinexor and eltanexor, two selective XPO1 inhibitors, in patient derived xenograft mice models of Wilms and MRT, and report on a case of successful treatment of a pediatric cancer patient. Overall design: RNASeq profiles of MRT cell lines and PLATESeq profiles of selinexor (or DMSO control) perturbation in multiple MRT cell lines.

本研究借助基于Master Regular的精准癌症医学工具OncoTarget，将XPO1鉴定为儿童肾肿瘤（肾母细胞瘤与恶性横纹肌样瘤[MRT]）中异常激活的、非癌基因编码的可靶向治疗脆弱位点。本研究证实，两种选择性XPO1抑制剂——塞利尼索（selinexor）与埃坦尼索（eltanexor）——在肾母细胞瘤与恶性横纹肌样瘤的患者来源异种移植小鼠模型中展现出显著的抗肿瘤活性，并报道了1例儿童癌症患者成功接受治疗的病例。实验整体设计：多种恶性横纹肌样瘤细胞系的RNASeq谱图，以及塞利尼索（或二甲基亚砜对照组）处理后多种恶性横纹肌样瘤细胞系的PLATESeq谱图。