Synergistic antitumor activity of regorafenib and lapatinib in preclinical models of human colorectal cancer

被引：30
|
作者：
Zhang, Wen-Ji [1 ,2 ]
Li, Yong [3 ]
Wei, Meng-Ning [1 ,2 ]
Chen, Yao [1 ,2 ]
Qiu, Jian-Ge [1 ,2 ]
Jiang, Qi-Wei [1 ,2 ]
Yang, Yang [1 ,2 ]
Zheng, Di-Wei [1 ,2 ]
Qin, Wu-Ming [1 ,2 ]
Huang, Jia-Rong [1 ,2 ]
Wang, Kun [1 ,2 ]
Zhang, Wen-Juan [4 ]
Wang, Yi-Jun [5 ]
Yang, Dong-Hua [5 ]
Chen, Zhe-Sheng [5 ,6 ]
Shi, Zhi [1 ,2 ]
机构：
[1] Jinan Univ, Dept Cell Biol, Guangzhou 510632, Guangdong, Peoples R China
[2] Jinan Univ, Inst Biomed, Natl Engn Res Ctr Genet Med, Guangdong Prov Key Lab Bioengn Med,Coll Life Sci, Guangzhou 510632, Guangdong, Peoples R China
[3] Guangdong Acad Med Sci, Guangdong Gen Hosp, Dept Gastrointestinal Surg & Gen Surg, Guangzhou 510080, Guangdong, Peoples R China
[4] Jinan Univ, Dept Prevent Med, Coll Med, Guangzhou 510632, Guangdong, Peoples R China
[5] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Hlth Sci, Queens, NY 11439 USA
[6] Jinan Univ, Coll Pharm, Guangdong Prov Key Lab Pharmacodynam Constituents, Guangzhou 510632, Guangdong, Peoples R China
来源：
CANCER LETTERS | 2017年 / 386卷
基金：
中国国家自然科学基金;
关键词：
Regorafenib; Lapatinib; Targeted therapy; Combination chemotherapy; Colorectal cancer; MULTIDRUG-RESISTANCE; BREAST-CANCER; DRUG-SENSITIVITY; PHASE-3; TRIAL; TUMOR-GROWTH; COLON-CANCER; INHIBITOR; CELLS; COMBINATION; MULTICENTER;
D O I：
10.1016/j.canlet.2016.11.011
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Regorafenib significantly prolongs overall survival in patients with metastatic colorectal cancer (mCRC), but the overall clinical efficacy of regorafenib remains quite limited. Combination chemotherapy is a potentially promising approach to enhance anticancer activity, overcome drug resistance, and improve disease-free and overall survival. The current study investigates the antitumor activity of regorafenib in combination with lapatinib in preclinical models of human CRC. Our results show improved antitumor efficacy when regorafenib is combined with lapatinib both in vitro and in vivo. Furthermore, pharmacokinetic analyses revealed that regorafenib and lapatinib do not influence on each plasma concentration. The finding that regorafenib in combination with lapatinib have synergistic activity warrants further clinical investigation of this beneficial combination as a potential treatment strategy for CRC patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：100 / 109
页数：10
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