title: Interaction of EGFR with the tumour microenvironment: implications for radiation treatment.
abstract: Treatment failure through radioresistance of tumours is associated with activation of the epidermal growth factor receptor (EGFR). Tumour cell proliferation, DNA-repair, hypoxia and metastases-formation are four mechanisms in which EGFR signalling has an important role. In clinical trials, a correlation has been demonstrated between high EGFR expression in tumours and poor outcome after radiotherapy. Inhibition of EGFR signalling pathways improves the effectiveness of radiotherapy of head and neck cancers by overcoming these main mechanisms of radioresistance. The fact that only a minority of the patients respond to EGFR inhibitors reflects the complexity of interactions between EGFR-dependent signalling pathways and the tumour microenvironment. Furthermore, many components of the microenvironment are potential targets for therapeutic interventions. Characterisation of the interaction of EGFR signalling and the tumour microenvironment is therefore necessary to improve the effectiveness of combined modality treatment with radiotherapy and targeted agents. Here, the current status of knowledge is reviewed and directions for future research are discussed.
authors.affiliation: Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: Monique M
authors.initials: MM
authors.lastname: Nijkamp
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.forename: Johannes H A M
authors.initials: JH
authors.lastname: Kaanders
mesh_terms: D015687:Cell Hypoxia; D049109:Cell Proliferation; D004260:DNA Repair; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D066246:ErbB Receptors
keywords: EGFR; Microenvironment; Radiotherapy