Novel Bone-Targeting Combination Therapy for Osteosarcoma Phase II

Project Summary AbstractThe overall aim of this project is to further develop a novel gemcitabine ibandronate conjugate alone and or as part of a combination therapy for the treatment of osteosarcoma and associated metastasesThe conjugate consists of chemically linked anticancer antimetabolite Gemcitabine and the bone homing bisphosphonate IbandronateThe novel conjugate directly addresses the limitations of conventional osteosarcoma therapies by concentrating drug at the site of bone lesions and offers potential improvements in efficacy and side effect profilesThis targeted delivery design provides for an effective concentration of a chemotherapy agent in bone while maintaining low systemic levelsIn Phasewe have demonstrated this conjugate offers synergies with Docetaxel and enables afold lower exposure to Gemcitabine while inhibiting cancer growth at a similar levelAs an added benefitthe drug appears to strengthen the bones and may reverse the deterioration of bone associated with bony malignanciesThis project looks specifically at optimizing the ability of the Gemcitabine Ibandronate conjugate alone or in combination with Docetaxel to treat a mouse model of osteosarcoma as compared to treatment with free Gemcitabine in combination with Docetaxel and tests the drugs in spontaneous osteosarcoma in a canine clinical trialThe specific aims of this Phase II project assess the tissue distribution and effects of the novel bone targeting conjugate alone and in combination with Docetaxel on local tumor burdenbone lysis and metastatic burden in an orthotopic osteosarcoma syngeneic murine model and spontaneous canine osteosarcomaThe successful completion of this project will guide the further development of this promising drug design concept and will ultimately result in therapeutic agents that will significantly improve cancer patient careresulting in increased quality of life and survival Project Narrative RelevanceOsteosarcomathe most common malignant bone tumor is highly metastaticgreat need exists to develop drugs for patients who present with metastatic disease or develop recurrent disease that leads to very poor prognosesThe long term goal of this research project is to further develop a promising drug specifically designed to deliver an anti cancer drug to bonewhile synergizing with standard of use drugs to improve patient outcomes such as survival and quality of lifeand reduce the numbers of amputations