title: Synergistic antitumor activity of regorafenib and lapatinib in preclinical models of human colorectal cancer.
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.
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Wen-Ji
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery & General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Meng-Ning
authors.initials: MN
authors.lastname: Wei
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Jian-Ge
authors.initials: JG
authors.lastname: Qiu
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Qi-Wei
authors.initials: QW
authors.lastname: Jiang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Di-Wei
authors.initials: DW
authors.lastname: Zheng
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Wu-Ming
authors.initials: WM
authors.lastname: Qin
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Huang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Preventive Medicine, College of Medicine, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, PR China. Electronic address: chenz@stjohns.edu.
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Chen
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China. Electronic address: tshizhi@jnu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D000077341:Lapatinib; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic; D010671:Phenylurea Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011799:Quinazolines / Q000493:pharmacokinetics / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011799:Quinazolines; D000077341:Lapatinib; C559147:regorafenib
keywords: Colorectal cancer; Combination chemotherapy; Lapatinib; Regorafenib; Targeted therapy