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

• Published in: Cancer letters 2017-02, Vol.386, p.100-109
• Main Authors: 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, MD, PhD, Shi, Zhi, MD, PhD
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - pharmacology; Animals; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis; Apoptosis - drug effects; Cancer therapies; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell growth; Cell Proliferation - drug effects; Colorectal cancer; Colorectal Neoplasms - blood; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Combination chemotherapy; Conflicts of interest; Dose-Response Relationship, Drug; Drug dosages; Drug Synergism; FDA approval; Female; Growth factors; HCT116 Cells; Hematology, Oncology and Palliative Medicine; HT29 Cells; Humans; Immunoglobulins; Inhibitory Concentration 50; Lapatinib; Mice, Inbred BALB C; Mice, Nude; Molecular Targeted Therapy; Neovascularization, Pathologic; Phenylurea Compounds - pharmacokinetics; Phenylurea Compounds - pharmacology; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - pharmacology; Pyridines - pharmacokinetics; Pyridines - pharmacology; Quinazolines - pharmacokinetics; Quinazolines - pharmacology; Regorafenib; Science; Software; Targeted therapy; Tumor Burden - drug effects; Xenograft Model Antitumor Assays
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2016.11.011

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.