Molecular Pathways: Anticancer Activity by Inhibition of Nucleocytoplasmic Shuttling

摘要: A dynamic distribution between nucleus and cytoplasm (nucleocytoplasmic shuttling) is one of the control mechanisms adapted by normal cells to regulate activity a variety molecules. Growing evidence suggests that dysregulation nucleocytoplasmic shuttling involved in promoting abnormal cell survival, tumor progression, drug resistance, associated with poor cancer prognosis. Aberrant may result from hyperactive status diverse signal-transduction pathways, such as PI3K-AKT MAPK or alterations general nuclear import/export machinery. Among large number molecules process, exportin XPO1, also known chromosome region maintenance 1, appears play particularly prominent role pathogenesis both hematological malignancies solid tumors. Given importance rapidly expanding knowledge this field, attempts have been made develop compounds able revert aberrant shuttling. promising new drug, KPT-330 (Selinexor), which belongs class XPO1 inhibitors called selective export, now being tested phase I/II clinical trials.