Selective inhibitors of nuclear export (SINE) in hematological malignancies

Arundhati Das; Guoqing Wei; Kaushal Parikh; Delong Liu

doi:10.1186/s40164-015-0002-5

Selective inhibitors of nuclear export (SINE) in hematological malignancies

Exp Hematol Oncol. 2015 Mar 1:4:7. doi: 10.1186/s40164-015-0002-5. eCollection 2015.

Authors

Arundhati Das¹, Guoqing Wei², Kaushal Parikh¹, Delong Liu³

Affiliations

¹ Department of Medicine, Westchester Medical Center, Valhalla, NY 10595 USA.
² Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Henan Cancer Hospital, Zhengzhou University, Zhengzhou, China.

Abstract

Regulated nucleo-cytoplasmic transport plays a major role in maintaining cellular homeostasis. CRM1 (chromosome region maintenance 1 or exportin 1 or XPO 1) is responsible for the nucleo-cytoplasmic transport of more than 200 proteins, including most of the tumor suppressor proteins (TSP). CRM1 is overexpressed in pancreatic cancer, osteosarcoma, glioma, cervical and hematological malignancies. This inspired the development of novel agents that selectively inhibit nuclear exportins (SINEs). In this review we focus on the significance of CRM1 in carcinogenesis and review the new development of SINE inhibitiors in hematological malignancies. Selinexor (KPT-330) as the first-in-human SINE agent represents this novel class of anti-cancer agents.

Keywords: KPT-330; SINE; Selective inhibitor of nuclear export; Slinexor.