Chen David J, Nirodi Chaitanya S
Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2201 Inwood Road, Dallas, TX 75390, USA.
Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6555-60. doi: 10.1158/1078-0432.CCR-07-1610.
The epidermal growth factor receptor (EGFR), which is frequently expressed in tumors of epithelial origin, is an important determinant of tumor responses to ionizing radiation. Elevated EGFR expression and activity frequently correlate with tumor resistance to radiotherapy in patients. EGFR is thought to confer tumor resistance to radiation through the activation of survival and cell proliferation pathways. Recent discoveries have identified a novel radioprotective function of EGFR which involves the radiation-induced nuclear translocation of the receptor and its interactions with the DNA-dependent protein kinase, a key component of the nonhomologous end-joining DNA repair pathway. Targeting the DNA repair function of EGFR may serve as a therapeutic model for sensitizing tumors to radiotherapy in patients.
表皮生长因子受体(EGFR)常在上皮源性肿瘤中表达,是肿瘤对电离辐射反应的重要决定因素。EGFR表达和活性升高常与患者肿瘤放疗抵抗相关。EGFR被认为通过激活生存和细胞增殖途径赋予肿瘤辐射抗性。最近的发现确定了EGFR一种新的辐射防护功能,该功能涉及受体的辐射诱导核转位及其与DNA依赖性蛋白激酶的相互作用,DNA依赖性蛋白激酶是非同源末端连接DNA修复途径的关键组成部分。靶向EGFR的DNA修复功能可能成为使患者肿瘤对放疗敏感的一种治疗模式。