SINE (selective inhibitor of nuclear export) - Translational science in a new class of anti-cancer agents

Abstract

Regulation of protein trafficking between the nucleus and cytoplasm represents a novel control point for antineoplastic intervention. Several proteins involved with cellular growth and survival depend on precise and timely positioning within the cell to fulfill their functions, and the nuclear membrane defines one of the most important compartmental barriers. Chromosome Region Maintenance 1, or exportin-1 (CRM1/XPO1), is involved with the export of more than 200 nuclear proteins, and has intriguingly been shown to have an increased expression in several tumor cell types. Selinexor (KPT-330) is a first-in-class selective inhibitor of nuclear export (SINE) to be developed for clinical use. Preclinical data has demonstrated antineoplastic activity of SINE compounds in many human solid and hematologic malignancies. The clinical development of Selinexor provides an excellent model for translational research.