All cancer cells originate from once normal cells in the human body. Combination of inherited and environmental factors permanently change the way normal cells behave and turn them into tumor cells. Tumor cells cease normal function and channel all of their resources for growth. There are effective drugs that can kill any type of cell in the laboratory setting, but since cancer cells originate from normal human tissues they still share a lot of common features. Therefore, current drugs designed for killing cancer cells also kill normal cells. This is the biggest limiting factor in cancer treatment today. The best way to overcome this problem is to isolate differences that are unique to cancer cells and attack them with selective weapons. The goal of our research is to hit such a novel target, called ezrin protein. This protein is relatively specific to cancer cells spreading in the body and plays a very important role in this process.

Osteosarcoma is a cancer of bone, which affects persons at any age, but most people affected are teenagers. Currently, patients who develop osteosarcoma undergo surgery and intensive chemotherapy for approximately one year. Patients usually die due to metastasis (lesions in other parts of the body in addition to the main tumor), not due to the initial tumor on their bones. If we can prevent spreading of tumor cells to other parts of the body, we can significantly improve survival in patients with osteosarcoma. Our laboratory has been investigating this problem in osteosarcoma and other childhood cancers. In this proposal, we seek to study small molecules that may inhibit osteosarcoma cells spreading to lung and its growth in this new location. Before these small molecules can be used in human clinical trials, they have to be proven effective and safe in some laboratory experiments. These experiments involve testing human osteosarcoma cells growing in plastic dishes and utilizing mouse models that resemble human disease. We have already made significant progress in identifying two lead compounds. This project will optimize our small molecules so that they can be applicable in human clinical trials. Development of these novel small molecules to drugs that can be given to patients can take 3-5 years. If they behave as anticipated, they can significantly improve the survival and quality of life in children with cancer.