The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia

• Published in: Clinical cancer research Vol. 23; no. 10; pp. 2528 - 2541
• Main Authors: Vercruysse, Thomas, De Bie, Jolien, Neggers, Jasper E, Jacquemyn, Maarten, Vanstreels, Els, Schmid-Burgk, Jonathan L, Hornung, Veit, Baloglu, Erkan, Landesman, Yosef, Senapedis, William, Shacham, Sharon, Dagklis, Antonis, Cools, Jan, Daelemans, Dirk
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.05.2017
• Subjects: Active Transport, Cell Nucleus - drug effects; Acute lymphoblastic leukemia; Animal models; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antitumor activity; Apoptosis; Apoptosis - drug effects; Biotechnology; Cancer; Cargo; Caspase; Cell death; Cell Line, Tumor; Clinical trials; CRISPR; CRISPR-Cas Systems; Experimental design; Exportin 1 Protein; Gene Editing; Genomes; Hematopoiesis; Humans; Inhibition; Inhibitors; Karyopherins - antagonists & inhibitors; Karyopherins - genetics; Leukemia; Lymphatic leukemia; Medical research; Mice; Nuclear transport; Pharmacology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Protein transport; Proteins; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Receptors, Cytoplasmic and Nuclear - genetics; Thiazoles - administration & dosage; Tumor cell lines; Xenograft Model Antitumor Assays; Xenografts

Human exportin-1 (XPO1) is the key nuclear-cytoplasmic transport protein that exports different cargo proteins out of the nucleus. Inducing nuclear accumulation of these proteins by inhibiting XPO1 causes cancer cell death. First clinical validation of pharmacological inhibition of XPO1 was obtained...