CLIN CANCER RES:贝伐单抗联合厄洛替尼对结直肠癌的疗效与RAS状态无关

2018-06-11 MedSci MedSci原创

结直肠癌中VEGF和EGFR信号通路存在广泛的交叉。但是,靶向VEGF和EGFR的单抗联合治疗活性较差,尤其是在RAS突变的患者中。之前的研究表明TKI类药物在单抗类药物耐药的结直肠癌模型中具有活性。CLIN CANCER RES近期发表了一篇文章,研究联合厄洛替尼是否可以增加贝伐单抗的活性。

结直肠癌中VEGF和EGFR信号通路存在广泛的交叉。但是,靶向VEGF和EGFR的单抗联合治疗活性较差,尤其是在RAS突变的患者中。之前的研究表明TKI类药物在单抗类药物耐药的结直肠癌模型中具有活性。CLIN CANCER RES近期发表了一篇文章,研究联合厄洛替尼是否可以增加贝伐单抗的活性。

作者在不同RAS状态和贝伐单抗敏感性的结直肠癌模型中研究贝伐单抗,厄洛替尼以及两者联合的抗肿瘤效果。使用免疫组化,Western blot和ELISA鉴定EGFR/VEGF通路活化情况。在不同RAS状态的结直肠癌细胞系中研究西妥昔单抗和厄洛替尼对EGF介导的迁移及EGFR-EGF反馈回路的影响。研究结果表明,在所有肿瘤模型中额外联合厄洛替尼均可以增加贝伐单抗活性,与RAS状态无关。贝伐单抗暴露伴随肿瘤细胞和肿瘤相关上皮细胞EGFR显着活化,导致胞内EGFR聚集,厄洛替尼可以增加这一效果。在细胞模型中,厄洛替尼可以增强EGF介导的功能,与RAS状态无关。而西妥昔单抗仅在RAS野生型细胞中具有活性。

文章最后认为,该研究结果为更好的理解贝伐单抗-厄洛替尼联合疗法提供了帮助。靶向相同信号通路的单抗和TKI类药物的不同活性在其他肿瘤类型中也可以进行研究。

原始出处:
Paul Mesange,Anail Bouygues,et al.Combinations of Bevacizumab and Erlotinib Show Activity in Colorectal Cancer Independent of RAS Status.CLIN CANCER RES.June 2018 doi:10.1158/1078-0432.CCR-17-3187

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