Chondrosarcoma is the second most common primary tumor of the bone having an incidence of 8 per million people in the US population over age 80. Research, particularly on cancer of the breast, has made great strides in curtailment of disease with chemo and radiation therapy. However, surgical removal remains the only viable option for the treatment of chondrosarcoma. New treatment options must to be identified to improve patient outcomes and decrease mortality associated with disease. For the most aggressive chondrosarcoma tumor, a grade IV, metastasis to the lung results in death in 80% of patients within 5 years of diagnosis. Here we propose to make quaternary ammonium analogues of novel chemotherapeutics. The positive charge of the ammonium substructure will allow targeting to the negatively charged cartilaginous matrix of chondrosarcoma. Our preliminary results indicate that our novel chemotherapeutic has highly potent activity against chondrosarcoma cells in animal models. In this phase I STTR application Terpenoid Therapeutics and our partners at the University of Iowa seek to show feasibility of treating this disease. Specifically, we propose two aims to accomplish this goal: 1) synthesize two novel quaternary ammonium analogues of our highly potent anti-cancer agents;and 2) test them in cell culture and animal models of chondrosarcoma. We believe that this strategy has a high likelihood of success in advancing a novel agent to the clinic for this orphan disease.
Chondrosarcoma is the second most common primary tumor of the bone having an incidence of 8 per million people in the US population over age 80. The aging of the population over the next twenty years will increase the number of people living with lower grade chondrosarcomas. Currently, surgical removal of the affected area is the only viable remedy for this disease. A chemotherapeutic intervention that could be used in conjunction with or instead of surgery is a high priority for this orphan indication.