Michael Ortiz, MD

Utilizing a novel tumor RNA analysis pipeline, we recently discovered that Wilms and rhabdoid tumors, two childhood kidney tumors, are unexpectedly dependent upon XPO1, a nuclear pore that pumps tumor suppressors out of the nucleus thereby inhibiting their function. We further showed that blocking XPO1, with a drug called Selinexor, was an effective strategy to shrink Wilms and rhabdoid tumors that we had established in mice. Selinexor had already completed a phase 1 study in children so we know the pediatric safety profile but a liquid formulation had not yet been available so younger children such as those with Wilms and rhabdoid tumors were not able to be evaluated. This project supports a phase 2 clinical trial in which we are evaluating how effective that the liquid suspension form of Selinexor is in patients with relapsed Wilms tumor, rhabdoid tumor, and other tumors for which XPO1 inhibition appears promising including a rare sarcoma called Malignant Peripheral Nerve Sheath Tumors (MPNST). We will enroll up to 9 young children as part of a safety assessment as well as up to 21 patients with Wilms tumor and up to 15 patients with other tumors as part of this study. Support from this grant will enable us to open the trial at 8 sites across the United States.