Use of Repurposed Drugs and Combinations of Proteasome Inhibitors and Topoisomerase Inhibitors for the Treatment of Chordoma

This technology includes a group of 20 drugs that can be further developed as a treatment for chordoma. Chordoma is a rare, slow-growing malignant tumor arising from remnants of the fetal notochord, with a high recurrence rate and no effective chemotherapy agents. These 20 drugs inhibited chordoma cell growth, with potencies ranging from 10 to 370 nM in the chordoma cell line UCH1 cells. These agents also had significant inhibitory effects on chordoma patient cells, C24, C25, and C32. Furthermore, a combination treatment of proteasome inhibitors, such as bortezomib and MG-132, with topoisomerase inhibitors, such as topotecan, rubitecan, camptothecin, doxorubicin, and daunomycin, significantly increased the therapeutic potency in the human chordoma cell line, UCH2, and primary chordoma patient cells, C24, C25, and C32.