Dr. Parekh on the Mechanism of Action of Selinexor in Myeloma

Samir Parekh, MD, associate professor of Medicine, Mount Sinai Health System, discusses the mechanism of action of selinexor in multiple myeloma.

Selinexor is an oral selective inhibitor of nuclear export (SINE). The drug has been tested in phase I/II trials and is currently under review by the FDA. In November 2018, the FDA granted a priority review designation to a new drug application for the inhibitor as a treatment for patients with penta-refractory multiple myeloma.

The drug has a unique mechanism of action in that it blocks a transporter called XPO1, says Parekh. The transporter is responsible for shuttling cargo proteins and messenger RNA between the nucleus and the cytoplasm. By blocking the export of these molecules, selinexor enables key changes in the dynamic that is responsible for tumor growth and suppression. Specifically, an increase in tumor suppressor proteins such as p53 and a reduction in oncogenic proteins within the NF-κBpathway are very important for myeloma growth. When selinexor is introduced, however, it essentially “shuts off” the cancerous cells and causes them to die, he says.