Biomaterial Database

Inhibition of c-ABL sensitizes breast cancer cells to the dual ErbB receptor tyrosine kinase inhibitor lapatinib (GW572016). 2011

Yuan-Hung Lo, and Po-Chun Ho, and Huajun Zhao, and Shao-Chun Wang

Department of Cancer and Cell Biology, 3125 Eden Ave., Cincinnati, OH 45267-0521, USA.

BACKGROUND The dual kinase inhibitor lapatinib (Tykerb) has been applied for advanced breast cancer. However, the effectiveness in the clinic has been elusive and the development of novel approaches to enhance the responsiveness is needed. In this study, we test whether the non-receptor tyrosine kinase c-Abl regulates the responsiveness of breast cancer cells to lapatinib and, if so, whether the combination treatment with lapatinib plus the c-ABL kinase inhibitor imatinib (STI571; Gleevec) can sensitize breast cancer cells to the treatment. METHODS The endogenous c-ABL kinase was silenced by RNA interference or inhibited by imatinib to test whether the co-treatment improves the responsiveness of the lapatinib-resistant breast cancer cell lines MDA-MB-468 and T47D, by measuring cell growth and cell-cycle progression. CONCLUSIONS The responsiveness to lapatinib can be improved by targeting the function of c-ABL, suggesting that combination treatment of lapatinib plus imatinib can lead to significant gains in therapeutic benefit.

UI	MeSH Term	Description	Entries
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D011743	Pyrimidines	A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D011799	Quinazolines	A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.	Quinazoline
D001943	Breast Neoplasms	Tumors or cancer of the human BREAST.	Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002453	Cell Cycle	The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.	Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D004354	Drug Screening Assays, Antitumor	Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.	Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068877	Imatinib Mesylate	A tyrosine kinase inhibitor and ANTINEOPLASTIC AGENT that inhibits the BCR-ABL kinase created by chromosome rearrangements in CHRONIC MYELOID LEUKEMIA and ACUTE LYMPHOBLASTIC LEUKEMIA, as well as PDG-derived tyrosine kinases that are overexpressed in gastrointestinal stromal tumors.	Alpha-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-tolu-p-toluidide,CGP 57148,CGP-57148,CGP57148B,Gleevec,Glivec,Imatinib,Imatinib Methanesulfonate,ST 1571,ST1571,STI 571,STI-571,STI571,CGP57148,Mesylate, Imatinib,Methanesulfonate, Imatinib
D000077341	Lapatinib	A quinazoline derivative that inhibits EPIDERMAL GROWTH FACTOR RECEPTOR and HER2 (RECEPTOR, ERBB-2) tyrosine kinases. It is used for the treatment of advanced or metastatic breast cancer, where tumors overexpress HER2.	GW 282974X,GW 572016,GW-282974X,GW-572016,GW282974X,GW572016,Lapatinib Ditosylate,N-(3-chloro-4-(((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-methylsulfonyl)ethyl)amino)methyl) -2-furyl)-4-quinazolinamine,Tykerb