Receptor Tyrosine Kinases As Targets For Enhancing Tumor Radiosensitivity

The advent of the modern era of molecularly targeted therapies in oncology has generated considerable excitement in the field of oncology. While there have been successes with molecularly targeted agents as monotherapies, most solid tumors display only a transient and modest response to single-targeted agents. As such, there has been significant effort in combining molecularly targeted agents with radiotherapy. Receptor tyrosine kinases (RTKs) play central roles in oncogenesis, stress sensitivity, tumor maintenance/progression, and clinical prognosis. Secondary to these roles, receptor tyrosine kinases are attractive targets for cancer therapy and specifically in combination with radiation therapy to enhance tumor radiosensitivity. Significant preclinical and clinical investigations have been performed to understand their roles in regulating the cellular response to radiation. A number of RTKs with relevance to radiation oncology have been identified including EGFR, VEGFR, IGF-1R, c-MET, and HER2. This chapter will highlight the preclinical and clinical findings associated with the combination of radiotherapy and inhibitors of the aforementioned receptors.