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• W2105177613 startingPage "1061" @default.
• W2105177613 abstract "HER-2 is a transmembrane, tyrosine kinase (TK) receptor whose overexpression is associated with adverse prognosis in breast cancer. The biological effects of HER-2 are mediated by kinase activity causing phosphorylation of tyrosine residues in the cytoplasmic domain of the receptor molecule, leading to activation of downstream growth-promoting pathways. Antibody-mediated inhibition by trastuzumab as well as TK inhibition are clinically effective anti-HER-2 strategies. Kinase inhibitors offer some potential therapeutic advantages over antibody-based therapies. Being small molecules, TK inhibitors (TKIs) have oral bioavailability and ability to cross the blood-brain barrier. Because of their different mode of action, TKIs may be able to overcome some of the mechanisms of trastuzumab resistance. Preclinical, and limited clinical data also suggest that TKIs and trastuzumab have synergistic activity. Lapatinib is the only TKI available for clinical use at present, but several molecules with anti-HER-2 activity have been identified and are undergoing evaluation. These differ in the spectrum of kinases that they inhibit, potency of HER-2 inhibition, pharmacokinetic properties, and toxicity profiles, and are at various stages of clinical development. In this article we summarize selected HER-2 TKIs approved for clinical use or in development for which clinical data are available." @default.
• W2105177613 created "2016-06-24" @default.
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• W2105177613 date "2009-11-01" @default.
• W2105177613 modified "2023-10-16" @default.
• W2105177613 title "Beyond Trastuzumab: Small Molecule Tyrosine Kinase Inhibitors in HER-2–Positive Breast Cancer" @default.
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• W2105177613 doi "https://doi.org/10.1634/theoncologist.2009-0142" @default.
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