1. Synergistic antitumor activity of regorafenib and lapatinib in preclinical models of human colorectal cancer.
- Author
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Zhang, Wen-Ji, Li, Yong, Wei, Meng-Ning, Chen, Yao, Qiu, Jian-Ge, Jiang, Qi-Wei, Yang, Yang, Zheng, Di-Wei, Qin, Wu-Ming, Huang, Jia-Rong, Wang, Kun, Zhang, Wen-Juan, Wang, Yi-Jun, Yang, Dong-Hua, Chen, Zhe-Sheng, and Shi, Zhi
- Subjects
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REGORAFENIB , *LAPATINIB , *COLON cancer , *COMBINATION drug therapy , *DRUG resistance , *PHARMACOKINETICS , *ANIMAL experimentation , *ANTHROPOMETRY , *ANTINEOPLASTIC agents , *APOPTOSIS , *CELL cycle , *CELL physiology , *CELLS , *DRUG therapy , *COLON tumors , *DRUG synergism , *DOSE-effect relationship in pharmacology , *HETEROCYCLIC compounds , *MICE , *NEOVASCULARIZATION inhibitors , *PYRIDINE , *UREA , *PROTEIN kinase inhibitors , *PATHOLOGIC neovascularization , *PHARMACODYNAMICS ,RECTUM tumors - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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