Talati Chetasi, Sweet Kendra L
Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, 33611, USA.
Int J Hematol Oncol. 2018 Sep 11;7(3):IJH04. doi: 10.2217/ijh-2018-0001. eCollection 2018 Oct.
Selective inhibitors of nuclear export (SINE) are emerging as a potentially efficacious therapeutic strategy for overcoming resistance to conventional chemotherapy for acute myeloid leukemia. SINE specifically block the protein Exportin 1, also known as chromosomal region maintenance 1, leading to nuclear retention of cargo proteins, including several tumor suppressor proteins. Selinexor, a first generation SINE, is currently in early phase clinical studies in various combinations with promising antileukemic and pro-apoptotic activity. Here we discuss the mechanism of action of SINEs and further elaborate on the clinical data available from the various trials in acute myeloid leukemia.
核输出选择性抑制剂（SINE）正逐渐成为一种潜在有效的治疗策略，用于克服急性髓系白血病对传统化疗的耐药性。SINE特异性阻断蛋白质输出蛋白1（也称为染色体区域维持蛋白1），导致包括几种肿瘤抑制蛋白在内的货物蛋白在细胞核内滞留。第一代SINE药物塞利尼索目前正处于早期临床研究阶段，与多种药物联合使用时具有良好的抗白血病和促凋亡活性。在此，我们讨论SINE的作用机制，并进一步阐述急性髓系白血病各种试验中可得的临床数据。
