|Awarded On||February 18, 2015|
|Title||Mechanisms of nuclear import and 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 protein cargos 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. The drug is in 12 Phase 1 and 2 clinical trials targeting many cancers. Selinexor is well tolerated, unlike an older CRM1 blocker named Leptomycin B (LMB), which was toxic in patients. Aim 1 of this proposal focuses on understanding how the two drugs act differently in cells. We will discover how Selinexor targets CRM1 to be destroyed or degraded and why this effect is absent with LMB. We will learn if this f...