Fellow: Kelly O'Connor

Mentor: Kelly Hume

Co-Mentor: Cheryl Balkman

DESCRIPTION (provided by applicant): 

Osteosarcoma is a common bone tumor seen in canine patients, accounting for 85% of canine bone tumors. Appendicular bones are most often affected. Affected dogs are extremely painful and pathologic fracture can occur. Standard of care therapy includes amputation of the affected limb and adjuvant intravenous carboplatin chemotherapy, in an attempt to delay the onset of metastatic disease. With this treatment approach, reported median survival times vary from 10 – 12 months. Ultimately, most dogs die as a consequence of metastatic disease. Investigation of alternate chemotherapy protocols has yet to yield an improvement in the currently expected outcomes. Finding an additional, efficacious anti-neoplastic agent to use in conjunction with carboplatin to prolong the survival times for canine osteosarcoma would be a significant contribution to treatment of this disease process. Tolerability of an additional agent would be of utmost concern in order to avoid any carboplatin delays or decreased quality of life in patients. Laverdia-CA1 (verdinexor), a selective inhibitor of nuclear export, is a promising agent to consider in conjunction with carboplatin. It is an oral medication administered twice weekly and its dose-limiting toxicity is distinct from that of carboplatin. Our research will determine if adjuvant therapy with carboplatin and Laverdia-CA1 is indicated for canine appendicular osteosarcoma. In Aim 1, we will conduct a clinical trial in pet dogs with histologically confirmed osteosarcoma to determine if combination therapy with carboplatin and Laverdia-CA1 is well-tolerated. In Aim 2, histologically confirmed canine appendicular osteosarcoma specimens will be tested for expression of XPO1 (exportin-1), which is the nuclear export targeted by Laverdia-CA1. Overexpression of this protein would strengthen the rationale for promotion of this therapeutic strategy in canine osteosarcoma.