Once initial hormone therapy has failed, median survival is only 6 months. Rebound of PSA suggests that the existence of nonandrogen factors in hormone refractory prostate cancers may upregulate PSA promoter activity in these cells. Osteosarcoma is a bone cancer that occurs primarily in teenagers and young adults. Five-year survival was less than 20 percent, and more than 80 percent of patients developed recurrent disease despite complete resection of the primary tumor. Recurrence of osteogenic sarcoma is usually manifested by metastatic disease.
Osteogenic sarcoma has a propensity to metastasize selectively to the lung parenchyma.
This behavior is likely biologically determined by a unique interaction between metastasizing cells and host tissue. A new agent with selective activity against osteogenic sarcoma, particularly one with a novel mechanism of action, could be a significant complement to current therapies for osteogenic sarcoma. A recent immunohistochemical study demonstrated that osteocalcin stained positive in primary osteoblastic osteosarcoma and chondroblastic osteosarcoma specimens, as well as in five of seven fibroblastic osteosarcomas. These observations support the development of osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma pulmonary metastases. Currently, we are combining several treatment strategies, including chemo gene therapy and local regional delivery of adenovirus, to target this lethal disease.