Breast Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Breast Cancer, including details on symptoms, genetics, screening, treatment, information.

A bifunctional targeted peptide that blocks HER-2 tyrosine kinase and disables mitochondrial function in HER-2-positive carcinoma cells.

Fantin VR, Berardi MJ, Babbe H, Michelman MV, Manning CM, Leder P

Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02215, USA. vfantin@genetics.med.harvard.edu

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.

Published 2 August 2005 in Cancer Res, 65(15): 6891-900.
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