Chapter 11 - Overcoming drug resistance in osteosarcoma and pancreatic adenocarcinoma with radioimmunotherapy

Abstract

Drug resistance presents an enormous problem in cancer which results in poor overall survival of cancer patients. Osteosarcoma and pancreatic adenocarcinoma are two examples of cancers where no meaningful progress in improving the survival of patients with metastatic disease has been achieved in the past 25years. Osteosarcoma is a primary cancer of the bone affecting mostly children and adolescents. Unlike some cancers, which share a common genetic signature, osteosarcoma demonstrates sweeping genetic variability from one tumor to the next, marked by complex karyotypes and substantial aneuploidy. Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in the United States which is projected to become oncological killer # 3 by 2020 by the American Cancer Society. This “silent killer” is characterized by its metastatic behavior before the primary tumor can be detected, resulting in a 5-year survival rate of less than 5%. For both osteosarcoma and PDAC, recent advances in immunotherapy have not resulted in any improvements in treating patients with metastatic disease. Targeted radionuclide therapy (TRT) utilizes cytocidal radiation delivered to the molecular targets on the cancer cells by antibodies, peptides, or small molecules. Recent regulatory approvals of TRT for treatment of metastatic prostate cancer and neuroendocrine tumors highlight TRT potential in treating cancers resistant to all other treatment modalities. In this chapter we discuss current and future applications of TRT toward treating osteosarcoma and PDAC.