BRAF和EGFR抑制剂联合用于BRAF突变型复发转移性结直肠癌PDXs模型的研究

发布时间：2018-06-05 03:39

本文选题：结直肠癌 + 复发转移　；参考：《中国癌症杂志》2017年07期

【摘要】：背景与目的:结直肠癌患者中BRAF基因突变的概率为5%~15%,临床预后明显差于无突变者。该研究将BRAF与表皮生长因子受体(epidermal growth factor receptor,EGFR)抑制剂联合用于BRAF V600E突变型复发转移性结直肠癌的患者来源异种移植(patient-derived xenografts,PDXs)模型,观察其安全性、可行性及疗效。方法:2016年1月—2016年12月,复旦大学附属肿瘤医院34例疑似结直肠癌术后复发或转移的患者利用CT引导下的穿刺活检方法获取组织标本,建立复发转移性结直肠癌的PDXs模型,筛选BRAF突变者传代培养至F2代进行药物实验,实验组分为BRAF抑制剂组(A组)、EGFR抑制剂组(B组)、BRAF和EGFR抑制剂联合组(C组)及安慰剂对照组(D组)。给药3周后处死实验动物,统计建模成功率及抑瘤率。结果:34例患者中共23例病理证实为结直肠癌复发或转移,成功建立16个PDX模型,建模成功率为69.6%(16/23)。共筛选出4例BRAF V600E基因突变者,成功建立4个BRAF突变型复发转移性结直肠癌的PDXs模型。实验组无明显药物毒性相关性死亡,实验组抑瘤率分别为21.57%、21.61%和66.81%,差异有统计学意义(P0.05)。结论:CT引导下的穿刺活检建立复发转移性结直肠癌的PDXs模型成功率高,针对EGFR和BRAF的双重打击治疗安全、可行,能够明显提高BRAF突变型结直肠癌的疗效。
[Abstract]:Background & objective: the probability of BRAF gene mutation in patients with colorectal cancer is 50.15%, and the clinical prognosis is significantly worse than that without mutation. In this study, BRAF was combined with epidermal growth factor receptor (EGFR) inhibitor in patients with BRAF V600E mutant recurrent and metastatic colorectal cancer. The model of patient-derived xenografts-PDXs was used to observe its safety, feasibility and efficacy. Methods: from January 2016 to December 2016, 34 patients suspected of recurrence or metastasis of colorectal cancer were obtained by CT-guided biopsy in Fudan University Cancer Hospital. The PDXs model of recurrence and metastasis of colorectal cancer was established. The experimental group was divided into BRAF inhibitor group (group A) and EGFR inhibitor group (group C) and placebo control group (group D). After 3 weeks of administration, the experimental animals were killed, and the success rate of modeling and tumor inhibition rate were statistically analyzed. Results Sixteen PDX models were successfully established in 23 patients with recurrence or metastasis of colorectal cancer confirmed by pathology in 34 patients. The success rate of modeling was 69.6% / 23%. Four patients with BRAF V600E gene mutation were selected and 4 PDXs models of BRAF mutation were successfully established. There was no obvious drug-toxicity related death in the experimental group. The tumor inhibition rate in the experimental group was 21.57% and 66.81%, respectively. The difference was statistically significant (P 0.05). Conclusion the success rate of PDXs model of recurrent and metastatic colorectal cancer established by puncture biopsy guided by 10% CT is high. It is safe and feasible to treat EGFR and BRAF with double blows, and can obviously improve the curative effect of BRAF mutant colorectal cancer.
【作者单位】：复旦大学附属肿瘤医院介入治疗科复旦大学上海医学院肿瘤学系;
【基金】：国家重点研发计划(2016YFC0106203)
【分类号】：R735.34

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