Radiation therapy (RT) is used to treat locally advanced cancer in many organ sites, especially primary tumors that are nonresectable. The combination of RT with standard chemotherapeutic agents (chemoRT) has improved clinical outcomes by both controlling local and micrometastatic disease. ChemoRT has become a standard treatment for many locally advanced cancers. However, toxicity to normal tissue and cancer cell resistance mechanisms limit the effectiveness of these combinations. Many pathways for cancer cell radiation resistance have been identified and may now be targeted with new therapeutic agents. The ability of targeted therapies to selectively increase cancer cells', but not normal tissues', sensitivity to chemoRT will improve clinical outcomes. The Molecularly Targeted Radiosensitization of Locally Advanced Cancers Specialized Program of Research Excellence (SPORE) focuses on targeting major mechanisms of radiation resistance in three different locally advanced cancers: pancreatic cancer, glioblastoma, and breast cancer. This is the first thematic SPORE focused on radiation therapy.
