期刊
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
卷 45, 期 12, 页码 1325-1332出版社
WILEY
DOI: 10.1111/eci.12557
关键词
Angiogenesis; angiotensin; angiotensin II receptor 1; breast cancer; colorectal cancer; polymorphisms
资金
- Plan Estatal de I + D + I, ISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion [PI10-00534, PI12-02017, PI13-00951]
- FEDER (European fund for regional development) funds
Background Currently, there are no predictive biomarkers for anti-angiogenic strategies in cancer, but response to anti-angiogenic drugs is associated with development of hypertension secondary to treatment. Therefore, this study explored the clinical relevance of genetic polymorphisms in some components of the renin-angiotensin system (RAS). Material and methods Genomic DNA was isolated from peripheral blood from 95 metastatic breast or colorectal cancer patients treated with bevacizumab, and AGTR1-A1166C (rs5186), AGT-M235T (rs699) SNPs and ACE I/D (rs4646994) polymorphisms were genotyped using RT-PCR. Circulating vascular endothelial grow factor and angiotensin converting enzyme (ACE) levels were analysed using ELISA kits. The antitumoral activity of bevacizumab was assayed in mice orthotopically xenografted with AGTR1-overexpressing breast cancer cells. Results The ACE IN/IN genotype was associated with a higher rate of disease progression compared to DEL/IN and DEL/DEL genotypes (36% vs. 11.1% P < 0.05). Similarly, AGTR1-1166A/A genotype was also associated with a higher rate of disease progression compared to AGTR1-1166A/C and AGTR1-1166C/C genotypes (24.4% vs. 2.7% P < 0.01). ACE IN/IN genotype was also found to be associated with shorter time to treatment failure compared to ACE IN/DEL and ACE DEL/DEL genotypes (14 weeks vs. 41.71, P = 0.033), whereas circulating ACE levels were found to be associated with a better response to bevacizumab treatment. Besides, in vivo experiments showed a significantly higher antitumoral activity of bevacizumab in tumours derived from AGTR1-overexpressing breast cancer cells. Conclusions A higher activity of ACE-angiotensin-II-AGTR1 axis is associated with a better response to bevacizumab, supporting that the RAS can be an important source of potential predictive markers of response to antiangiogenic drugs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据