阿帕替尼治疗恶性肿瘤的临床研究进展

随着抗血管生成靶向治疗的发展，作用于血管内皮生长因子（vascular endothelial growth factor，VEGF）及其血管内皮生长因子受体（vascular endothelial growth factor receptor ，VEGFR）信号通路的抗肿瘤药物越来越受到广泛的关注。血管内皮细胞生长因子受体- 2（vascular endothelial growth factor receptor 2，VEGFR- 2）抑制剂阿帕替尼是一种高效抗血管生成药物，是最新上市的口服分子靶向抗肿瘤药物之一。阿帕替尼在人体生物利用度高，安全性及耐受性良好。上市前后一系列大规模的随机、对照临床试验证实阿帕替尼在多种恶性肿瘤中具有一定的客观有效率和生存获益，如胃癌、非小细胞肺癌（non-small cell lung cancer ，NSCLC ）、乳腺癌等，尤其是在胃癌中。2014年该药在中国批准上市应用于临床治疗晚期胃癌。目前正在进行胃癌、肺癌、肝癌、食管癌、结直肠癌等多种恶性肿瘤的Ⅱ/ Ⅲ期临床试验，以探讨其单独或联合抗肿瘤活性。本文就阿帕替尼抗肿瘤机制、对不同类型肿瘤的临床疗效、安全性及不良反应、药物相互作用、耐药及生物标志物等最新研究进展进行综述，以加深对该药抗肿瘤应用的了解，为临床实践提供参考，并期望为恶性肿瘤患者的治疗带来一些新的选择。 

Clinical research advances of apatinib in the treatment of malignancies

Antitumor drugs that target the signaling of vascular endothelial growth factor and its receptors have attracted increasing attention with the development of antiangiogenic targeted therapy. Apatinib is a second-generation vascular endothelial growth factor receptor-2 inhibitor and a potent antiangiogenic agent. Apatinib is one of the recent oral molecular targeted anti tumor drugs. Clinical studies have indicated that apatinib exhibits high bioavailability and a tolerable safety profile. A series of large-scale randomized and controlled clinical trials before and after the release of the drug in the market have demonstrated encouraging objective response rate and survival benefit across a broad range of malignancies, including non-small cell lung cancer, breast cancer, and gastric cancer. Apa-tinib was approved and launched in China in 2014 as a subsequent-line treatment for patients with advanced gastric cancer. Apatinib is currently undergoing phase II/III clinical trials for the treatment of numerous cancer types, such as gastric carcinoma, lung cancer, he-patocellular carcinoma, esophageal cancer, and colorectal cancer. These clinical trials are conducted to determine the antitumor activi-ty of apatinib when administrated alone or in combination with other therapies. This review summarizes the latest research progress of apatinib, including antitumor mechanisms, clinical effects on different tumor types, safety profile and adverse effects, drug interac-tions, as well as drug resistance and biomarkers. This article presents a deeper understanding of the clinical application of apatinib in anti tumor treatment, and provides reference for future clinical practice in therapeutic options for cancer patients.