This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fantin, V. R. Articles by Leder, P. Search for Related Content PubMed PubMed Citation Articles by Fantin, V. R. Articles by Leder, P.

A Bifunctional Targeted Peptide that Blocks HER-2 Tyrosine Kinase and Disables Mitochondrial Function in HER-2-Positive Carcinoma Cells

¹ Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute and ² Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Valeria R. Fantin, Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, Room 356, New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02215. Phone: 617-432-7578; E-mail: vfantin{at}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.

This article has been cited by other articles:

				V. R. Fantin, A. Loboda, C. P. Paweletz, R. C. Hendrickson, J. W. Pierce, J. A. Roth, L. Li, F. Gooden, S. Korenchuk, X. S. Hou, et al. Constitutive Activation of Signal Transducers and Activators of Transcription Predicts Vorinostat Resistance in Cutaneous T-Cell Lymphoma Cancer Res., May 15, 2008; 68(10): 3785 - 3794. [Abstract] [Full Text] [PDF]

				B. Law, L. Quinti, Y. Choi, R. Weissleder, and C.-H. Tung A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity. Mol. Cancer Ther., August 1, 2006; 5(8): 1944 - 1949. [Abstract] [Full Text] [PDF]

				C. Cai, P. Lin, K.-H. Cheung, N. Li, C. Levchook, Z. Pan, C. Ferrante, G. L. Boulianne, J. K. Foskett, D. Danielpour, et al. The Presenilin-2 Loop Peptide Perturbs Intracellular Ca2+ Homeostasis and Accelerates Apoptosis J. Biol. Chem., June 16, 2006; 281(24): 16649 - 16655. [Abstract] [Full Text] [PDF]