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.
Thesaurus Terms: Affect;Aged, 80 And Over;Aging;Ammonium;Analog;Animal Model;Antineoplastic Agents;Area;Base;Biological Assay;Biological Markers;Bone;Cell Culture Techniques;Cell Line;Cells;Cessation Of Life;Charge;Chemical Standard;Chemotherapy;Chondroma;Chondrosarcoma;Clinic;Data;Diagnosis;Disease;Disease Model;Dose;Drug Delivery Systems;Excision;Extracellular Matrix;Feasibility Studies;Functional Group;Goals;Growth;Human;Immunocompromised Host;Improved;Incidence;Indoles;Innovation;Interest;Intervention;Iowa;Lead;Life;Malignant - Descriptor;Malignant Breast Neoplasm;Melphalan;Metastatic Neoplasm To The Lung;Methods;Modality;Mortality Vital Statistics;Mouse Model;Mus;Neoplasms;Novel;Operative Surgical Procedures;Orphan;Osteosarcoma;Outcome;Patients;Phase;Population;Primary Neoplasm;Proteoglycan;Public Health Relevance;Radiation Therapy;Rare Diseases;Rattus;Research;Research Design;Resources;Site;Skeletal;Small Business Technology Transfer Research;Staging;Standard Care;Success;Terpenes;Tertiary Amine;Testing;Therapeutic;Tissue Sample;Treatment Strategy;Tumor;Tumor Burden;Tumor Growth;Universities;Xenograft Procedure;
