|Awarded On||February 21, 2018|
|Title||Mechanisms of Nuclear Export in Cancer|
|Award Mechanism||Individual Investigator|
|Institution/Organization||The University of Texas Southwestern Medical Center|
|Principal Investigator/Program Director||Yuh Min Chook|
|Cancer Sites||All Sites|
CRM1 transports about 1000 different protein cargos, including many tumor suppressors, out of the cell nucleus. In cancer, many tumor suppressor cargos are inappropriately transported by CRM1, thus preventing cancer cell death and causing resistance to therapy. Anti-CRM1 drug Selinexor reverts cargo misplacement and causes cancer cell death. Selinexor is in more than 30 Phase 1, 2, and 3 clinical trials for various cancers. 2nd generation drug KPT-8602 is also in a Phase 1/2 study for multiple myeloma. Selinexor and KPT-8602 are well tolerated, unlike an older toxic CRM1 blocker named Leptomycin B (LMB) because of a key difference (discovered by our laboratory) in how they block CRM1. Seline...