预测贝伐珠单抗抗肿瘤治疗效果的生物学标记物

摘要

贝伐珠单抗已被用于多种恶性肿瘤的治疗,但仍没有一个公认的普遍适用的疗效预测指标.目前除了以影像学、副反应作为预测因子外,很多研究集中在对生物学标记物的筛选上.循环标记物中血管内皮生长因子(vascular endothelial growth factor,VEGF)水平对疗效的预测没有定论,而治疗前高水平可溶性血管内皮生长因子受体(soluble vascular endothelial growth factor receptor,sVEGFR)及低水平m管细胞间粘附因子-1、E-选择素、血管紧张素-2预示着治疗反应更好.肿瘤组织免疫组化方面,研究发现治疗前磷酸化VEGFR2与VEGFR2比值高或低表达碳酸酐酶9(carbonicanhydrase9,CA9)、CD31-微m管密度(CD31-microvesseldensty,CD31-MVD)患者的疾病控制率高.另外基因方面的研究显示含有VEGF-634CC和VEGF-1498TT者副反应较少,而携带VEGFR2H472Q变异型基因者出现副反应的几率高.综上,要找到合适的生物学标记物来预测贝伐珠单抗抗肿瘤治疗的效果,需要进一步的基础研究去发现更特异的作用位点及更大规模的临床试验去验证.%Bevacizumab, the monoclonal antibody of vascular endothelial growth factor (VEGF) has been applied to the therapy of several neoplasms, but an appropriate biomarker to predict the efficacy has not been found. Those markers can originate from peripheral circulation, tumor tissue and genes. Some researches have found that low level of vascular cell adhesion molecule-1 (VCAM-l), E-selectin, angiopoietin 2 (Ang-2) in circulation or carbonic anhydrase 9 (CA9), CD31-microvessel density (CD31-MVD) in tumor tissue can predict better activity of bevacizumab. Moreover, high level of soluble VEGFR2 (sVEGFR2) in circulation or the ratio of phosphorylated-VEGFR2 (p-VEGFR2) and VEGFR2 in tumor tissue increasing has the same predictive function. As to the gene, VEGF-634 CC, VEGF-1498 TT and VEGFR2 H472Q.are only related to the side effct. Thus more clinical tirals and basic researches should be performed to find out effective biomarkers in bevacizumab's therapy.