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Tytuł pozycji:

Comparative analysis of evolutionarily conserved motifs of epidermal growth factor receptor 2 (HER2) predicts novel potential therapeutic epitopes.

Tytuł:
Comparative analysis of evolutionarily conserved motifs of epidermal growth factor receptor 2 (HER2) predicts novel potential therapeutic epitopes.
Autorzy:
Xiaohong Deng
Xuxu Zheng
Huanming Yang
José Manuel Afonso Moreira
Nils Brünner
Henrik Christensen
Temat:
Medicine
Science
Źródło:
PLoS ONE, Vol 9, Iss 9, p e106448 (2014)
Wydawca:
Public Library of Science (PLoS), 2014.
Rok publikacji:
2014
Kolekcja:
LCC:Medicine
LCC:Science
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1932-6203
Relacje:
http://europepmc.org/articles/PMC4156330?pdf=render; https://doaj.org/toc/1932-6203
DOI:
10.1371/journal.pone.0106448
Dostęp URL:
https://doaj.org/article/803dcdff504042eaa7ccf8ee944dcd97  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.803dcdff504042eaa7ccf8ee944dcd97
Czasopismo naukowe
Overexpression of human epidermal growth factor receptor 2 (HER2) is associated with tumor aggressiveness and poor prognosis in breast cancer. With the availability of therapeutic antibodies against HER2, great strides have been made in the clinical management of HER2 overexpressing breast cancer. However, de novo and acquired resistance to these antibodies presents a serious limitation to successful HER2 targeting treatment. The identification of novel epitopes of HER2 that can be used for functional/region-specific blockade could represent a central step in the development of new clinically relevant anti-HER2 antibodies. In the present study, we present a novel computational approach as an auxiliary tool for identification of novel HER2 epitopes. We hypothesized that the structurally and linearly evolutionarily conserved motifs of the extracellular domain of HER2 (ECD HER2) contain potential druggable epitopes/targets. We employed the PROSITE Scan to detect structurally conserved motifs and PRINTS to search for linearly conserved motifs of ECD HER2. We found that the epitopes recognized by trastuzumab and pertuzumab are located in the predicted conserved motifs of ECD HER2, supporting our initial hypothesis. Considering that structurally and linearly conserved motifs can provide functional specific configurations, we propose that by comparing the two types of conserved motifs, additional druggable epitopes/targets in the ECD HER2 protein can be identified, which can be further modified for potential therapeutic application. Thus, this novel computational process for predicting or searching for potential epitopes or key target sites may contribute to epitope-based vaccine and function-selected drug design, especially when x-ray crystal structure protein data is not available.

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