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癌症严重危害人类健康,根据美国癌症协会2013年统计报告公布,目前全世界范围内每死亡8人,其中就有1人死于癌症。在2008年,全世界约有1270万人被诊断出患有癌症,约760万人死亡。预计到2030年,新发癌症患者将达到2130万人,将有1310万人死亡。
癌症的传统治疗手段主要包括手术、放疗和化疗,这些方法虽然已大幅度改善肿瘤的治疗效果,但仍存在不良反应、缺乏特异性、容易对正常组织产生损伤等缺点。因此,仍需要寻找更有效的治疗方法来改善治疗效果。
随着肿瘤生物学的发展,有研究发现,某些基因的过度表达或突变会对肿瘤的生物学性质以及治疗效果有显著影响,提出通过阻断这些基因来控制和治疗肿瘤,这就是分子靶向治疗[1]。即针对不同的靶点,选择不同的靶向药物进行特异性地治疗。其中,表皮生长因子受体(epidermal growth factor receptor,EGFR)在实体瘤中的过度表达与肿瘤发展及转移密切相关[2-3]。然而,采用EGFR进行分子靶向治疗能够取得良好疗效的患者比例并不高。临床实验显示,Erlotinib和Gefitinib治疗非小细胞肺癌(non-small-cell carcinoma,NSCLC)仅对10%~15%的患者有效[4]。卵巢癌、头颈癌、食道癌、宫颈癌、膀胱癌、乳癌、结直肠癌、胃癌和子宫内膜癌的不良预后均与EGFR的过度表达以及突变状态相关[5]。可见在靶向治疗前,对患者进行EGFR表达水平的评估十分必要。目前,临床上用于检测EGFR表达水平的方法主要有活检和血清学检测[6],但都存在一定的缺陷。相比之下,核医学显像能够无创地对肿瘤进行分子水平上的评价,其灵敏度高,可重复性强,能为临床治疗提供十分有利的依据。目前,检测EGFR的药物主要分为2类:单克隆抗体和小分子酪氨酸激酶抑制剂[7]。
靶向表皮生长因子受体分子探针研究进展
Research progresses on molecular probes targeting epidermal growth factor receptor
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摘要: 许多恶性肿瘤细胞的增殖、转移以及不良的预后已被证实与表皮生长因子受体(EGFR)的过度表达相关。目前,针对这个靶点,美国食品和药物管理局已经批准了多个靶向EGFR药物,如吉非替尼、厄洛替尼,但治疗效率总体偏低。核医学显像能够在分子水平上评价EGFR的表达水平及其突变程度,从而为临床个性化治疗提供有力依据。笔者简述靶向EGFR分子探针及其存在的缺点,以期为进一步研究提供帮助。
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关键词:
- 表皮生长因子受体 /
- 体层摄影术, 发射型计算机, 单光子 /
- 正电子发射断层显像术 /
- 分子探针
Abstract: Overexpression of epidermal growth factor receptor(EGFR)has been confirmed to be associated with cell malignancy, metastasis and poor prognosis. Against this target, several drugs have been approvaled, such as gefitinib and erlotinib. However, the therapeutic effect was not satisfied. PET/ SPECT imaging can evaluate the expression and mutation of EGFR at molecular level to provide the basis for individual treat. This article is an overview of the progress of PET/SPECT molecular probes targeting EGFR and related problems in order to provide help for further research. -
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