title: EGFR targeted therapies and radiation: Optimizing efficacy by appropriate drug scheduling and patient selection.
abstract: The epidermal growth factor receptor (EGFR) plays an important role in tumor progression and treatment resistance for many types of malignancies including head and neck, colorectal, and nonsmall cell lung cancer. Several EGFR targeted therapies are efficacious as single agents or in combination with chemotherapy. Given the toxicity associated with chemoradiation and poor outcomes seen in several types of cancers, combinations of EGFR targeted agents with or without chemotherapy have been tested in patients receiving radiation. To date, the only FDA approved use of an anti-EGFR therapy in combination with radiation therapy is for locally advanced head and neck cancer. Given the important role EGFR plays in lung and colorectal cancer and the benefit of EGFR inhibition combined with chemotherapy in these disease sites, it is perplexing why EGFR targeted therapies in combination with radiation or chemoradiation have not been more successful. In this review we summarize the clinical findings of EGFR targeted therapies combined with radiation and chemoradiation regimens. We then discuss the interaction between EGFR and radiation including radiation induced EGFR signaling, the effect of EGFR on DNA damage repair, and potential mechanisms of radiosensitization. Finally, we examine the potential pitfalls with scheduling EGFR targeted therapies with chemoradiation and the use of predictive biomarkers to improve patient selection.
authors.affiliation: University of Michigan, Department of Radiation Oncology, Ann Arbor, MI, United States; Ann Arbor Veterans Affairs Hospital, Department of Radiation Oncology, Ann Arbor, MI, United States.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Cuneo
authors.affiliation: University of Michigan, Department of Radiation Oncology, Ann Arbor, MI, United States.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Nyati
authors.affiliation: University of Michigan, Department of Radiation Oncology, Ann Arbor, MI, United States.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Ray
authors.affiliation: University of Michigan, Department of Radiation Oncology, Ann Arbor, MI, United States. Electronic address: tsl@med.umich.edu.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068818:Cetuximab / Q000008:administration & dosage / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006258:Head and Neck Neoplasms / Q000628:therapy; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy; D009369:Neoplasms / Q000628:therapy*; D018579:Patient Selection; D012004:Rectal Neoplasms / Q000628:therapy
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Chemoradiation; Combined modality therapy; EGFR; Epidermal growth factor receptor; Personalized medicine; Radiation