Preclinical strategies for testing of targeted radiosensitizers

Use of radiation for cancer therapy began shortly after the discovery of X-rays in 1895. Technological advances over the ensuing 120 years have enabled the development of sophisticated treatment systems, and radiation therapy remains an important component of cancer treatment, with more than 50% of all cancer patients receiving radiation therapy at some point in the course of the disease. In the 1960s and 1970s, combining chemotherapy with radiation was found to have synergistic anti-cancer effects for patients with advanced cancer. In more recent years, the advent of molecular biology has facilitated the development of specific drugs for molecular targets involved in neoplastic processes, giving rise to targeted therapy. Although the radiosensitization capabilities of some targeted agents have led to improved clinical outcomes in some cases, numerous clinical trials of targeted therapies with radiation have failed to demonstrate such improvements. One reason for this failure may be the use of poorly designed and reported preclinical studies as the rationale for undertaking large, expensive, and ultimately unsuccessful clinical trials. In this chapter, we introduce current preclinical screening methods for radiosensitizers, review current guidelines and recommendations for the standardization of preclinical studies, and discuss future opportunities in the era of precision radiation oncology.