Galinski Basia, Alexander Thomas B, Mitchell Daniel A, Chatwin Hannah V, Awah Chidiebere, Green Adam L, Weiser Daniel A
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599, USA.
Cancers (Basel). 2021 Dec 7;13(24):6161. doi: 10.3390/cancers13246161.
Overexpression of Exportin-1 (), 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.
核输出蛋白1（Exportin-1，XPO1）是核质转运的关键调节因子，其过表达与多种成人恶性肿瘤患者的不良预后相关。在临床试验中，使用塞利尼索靶向XPO1已显示出有前景的结果，促使美国食品药品监督管理局（FDA）批准其用于多种复发/难治性癌症。然而，儿童癌症中XPO1的生物学特性和对塞利尼索的敏感性直到最近才开始被探索。在这篇综述中，我们将聚焦于儿童癌症和成人癌症在与XPO1及关键转运蛋白相关方面的生物学差异。我们还将进一步探讨XPO1抑制剂在儿童癌症临床前和临床开发的现状。最后，我们将概述整合XPO1抑制以改善儿童癌症患者预后的潜在有前景的未来治疗策略以及潜在挑战。
