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Your search keyword '"Fang, Yueh-Fu"' showing total 6 results
Start Over Author "Fang, Yueh-Fu" Publisher american association for cancer research
6 results on '"Fang, Yueh-Fu"'

6. Definition of PKC-α, CDK6, and MET as therapeutic targets in triple-negative breast cancer.

Author

Hsu YH, Yao J, Chan LC, Wu TJ, Hsu JL, Fang YF, Wei Y, Wu Y, Huang WC, Liu CL, Chang YC, Wang MY, Li CW, Shen J, Chen MK, Sahin AA, Sood A, Mills GB, Yu D, Hortobagyi GN, and Hung MC

Subjects
Animals, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation genetics, Female, Gene Expression Regulation, Neoplastic drug effects, Gene Expression Regulation, Neoplastic genetics, Humans, MCF-7 Cells, Mice, Mice, Nude, Neoplastic Stem Cells drug effects, Protein Kinase Inhibitors pharmacology, Protein Serine-Threonine Kinases genetics, Survival Rate, Triple Negative Breast Neoplasms drug therapy, Cyclin-Dependent Kinase 6 genetics, Protein Kinase C-alpha genetics, Proto-Oncogene Proteins c-met genetics, Triple Negative Breast Neoplasms genetics
Abstract

Triple-negative breast cancer (TNBC) is a highly heterogeneous and recurrent subtype of breast cancer that lacks an effective targeted therapy. To identify candidate therapeutic targets, we profiled global gene expression in TNBC and breast tumor-initiating cells with a patient survival dataset. Eight TNBC-related kinases were found to be overexpressed in TNBC cells with stem-like properties. Among them, expression of PKC-α, MET, and CDK6 correlated with poorer survival outcomes. In cases coexpressing two of these three kinases, survival rates were lower than in cases where only one of these kinases was expressed. In functional tests, two-drug combinations targeting these three kinases inhibited TNBC cell proliferation and tumorigenic potential in a cooperative manner. A combination of PKC-α-MET inhibitors also attenuated tumor growth in a cooperative manner in vivo. Our findings define three kinases critical for TNBC growth and offer a preclinical rationale for their candidacy as effective therapeutic targets in treating TNBC., (©2014 American Association for Cancer Research.)

Published
2014
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