Breast Cancer
Online ISSN : 1880-4233
Print ISSN : 1340-6868
ISSN-L : 1340-6868
Review Articles
Antitumor Protein Therapy; Application of the Protein Transduction Domain to the Development of a Protein Drug for Cancer Treatment
Hiroshi HaradaShinae Kizaka-KondohMasahiro Hiraoka
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JOURNAL FREE ACCESS

2006 Volume 13 Issue 1 Pages 16-26

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Abstract
The genomic information obtained through the human genome project has been accelerating the analysis of the functions of various disease relevant genes. The high molecular weight biomolecules, including oligonucleotides, antisense nucleotides, small interference RNA and peptides, as well as genes (cDNA) and proteins, are becoming increasingly important for the development of molecular therapies. However, the potential of such information-rich macromolecules for therapeutic use has been limited by the poor permeability across the lipid bilayer of the cellular plasma membrane. Over the past decade, a unique activity of oligopeptides, known as protein transduction domains (PTDs) or cell penetrating peptides (CPPs), has made it possible to transduce biologically active macromolecules into living cells in vitro by conjugating a PTD to the desired macromolecule. Furthermore, this activity has also enabled the systemic delivery of bioactive macromolecules to all tissues in living animals. However, we are now confronted with the next difficulty delivering the macromolecules specifically to the therapeutic targets in vivo. In this review, we focus on the application of PTD to develop antitumor macromolecules and introduce several representative strategies to discriminate between tumor and normal tissue. In addition, we discuss the unique characteristics of breast cancer, which are expected to facilitate the application of PTD to develop novel protein therapy for breast cancer.
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© 2006 by The Japanese Breast Cancer Society
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