靶向VEGFR2抗体研究进展

Progress of Anti-VEGFR2 Pathway Antibody

恶性肿瘤是全球范围内严重危害人类健康的疾病,并且发病率逐年上升。血管生成是肿瘤发生发展最重要的过程之一,90%的实体瘤都依赖功能性的血管网络提供氧气和营养。血管生成主要由血管内皮生长因子(VEGFs)和血管内皮生长因子受体(VEGFRs)调节,而通过单克隆抗体阻断VEGF/VEGFR2相互作用能够显著抑制肿瘤生长,是一种非常有前景的抗肿瘤策略。雷莫芦作为目前惟一一款上市的靶向VEGFR2的抗体药物,在多种癌症中取得了良好的临床效果。然而单靶点的治疗方法易产生耐药性及不良反应,多功能、多靶点的治疗策略如联合用药等成为目前肿瘤治疗的主流。同时,VEGFR2由于其在肿瘤细胞及肿瘤血管高表达的特性也成为了双特异性抗体良好的靶标。因此文章就靶向VEGFR2抗体的研究现状、挑战及以其为基础的多靶点治疗策略进行综述,并对肿瘤治疗的未来发展趋势进行展望。

Malignant tumor is a kind of deadly disease that threatens human health severely,and its incidence is on rise year by year.Angiogenesis is one of the most pivotal progresses of tumor growth,and more than 90%of solid tumors are dependent on a functional vascular network for the supply of oxygen and nutrients.In addition,angiogenesis is regulated principally by interactions between vascular endothelial growth factors(VEGFs)and VEGF receptors(VEGFRs).The approach of blocking the interaction of VEGF and VEGFR2 significantly inhibits tumor growth and has become a promising anticancer strategy.Ramucirumab,a fully humanized monoclonal antibody,was the only drug that targeted to VEGFR2 approved by FDA for the treatment of human cancer and has achieved excellent clinical outcome.However,mono-target therapy may lead to drug resistance and side effects.As a result,mutifunction and muti-target therapeutic methods like combination therapy have become a major trend for the treatment of malignant tumor.Because of the high expression on tumor cell and tumor vascular but low expression on normal tissue,VEGFR2 becomes a great target applied in bi-specific antibody.Thus,this article reviews the progress,challenge of anti-VEGFR2 antibody as well as its application in the field of muti-target treatment,and also makes a prospect for the future tumor treatment.