Radiation Oncology and Molecular-Targeted Therapy for EGFR and its Signal Transduction Pathways: Molecular Basis and Clinical Application for Improvement of Radiotherapeutic Outcomes

Tetsuo      Akimoto; Norio      Mitsuhashi

Abstract

Molecular target-based drugs have been expected as promising drugs in cancer treatment, and clinical trials using combined radiation therapy plus molecular target-based drugs have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and these drugs is indispensable. Preclinical data have already demonstrated synergistic enhancement of radiation-induced cell killing by several molecular target-based drugs, such as EGFR inhibitors. Among these, the effect of drugs targeted against receptor tyrosine kinase and its signal transduction pathways on the radiosensitivity has been intensively investigated. In this review, established and potential molecular targets for potentiation of radiation-induced cell killing are summarized, especially focusing on EGFR and its signal transduction pathways; also, clinical trials of combined radiation therapy plus molecular-target drug therapy are summarized.

Keywords: EGFR, molecular target, radiation, radiosensitivity