A bifunctional targeted peptide that blocks HER-2 tyrosine kinase and disables mitochondrial function in HER-2-positive carcinoma cells
VR Fantin, MJ Berardi, H Babbe, MV Michelman… - Cancer research, 2005 - AACR
VR Fantin, MJ Berardi, H Babbe, MV Michelman, CM Manning, P Leder
Cancer research, 2005•AACRThe HER-2 oncoprotein is commonly overexpressed in a variety of human malignancies and
has become an attractive antitumor target. A number of strategies to inhibit the HER-2
receptor tyrosine kinase are currently the focus of intensive preclinical and clinical research.
In the present study, we have engineered a bifunctional peptide, BHAP, which consists of
two modular domains: a HER-2-targeting/neutralizing domain and a mitochondriotoxic,
proapoptotic domain. The chimeric peptide is biologically active and capable of selectively …
has become an attractive antitumor target. A number of strategies to inhibit the HER-2
receptor tyrosine kinase are currently the focus of intensive preclinical and clinical research.
In the present study, we have engineered a bifunctional peptide, BHAP, which consists of
two modular domains: a HER-2-targeting/neutralizing domain and a mitochondriotoxic,
proapoptotic domain. The chimeric peptide is biologically active and capable of selectively …
Abstract
The HER-2 oncoprotein is commonly overexpressed in a variety of human malignancies and has become an attractive antitumor target. A number of strategies to inhibit the HER-2 receptor tyrosine kinase are currently the focus of intensive preclinical and clinical research. In the present study, we have engineered a bifunctional peptide, BHAP, which consists of two modular domains: a HER-2-targeting/neutralizing domain and a mitochondriotoxic, proapoptotic domain. The chimeric peptide is biologically active and capable of selectively triggering apoptosis of HER-2-overexpressing cancer cells in culture, even those previously described as Herceptin resistant. Furthermore, BHAP slows down growth of HER-2-overexpressing human mammary xenografts established in SCID mice. This approach can be extended to the development of tailored targeted chimeric peptides against a number of overexpressed cellular receptors implicated in the development and progression of cancer.
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