Abstract

Doc number: 397

Abstract

Background: The epidermal growth factor receptor family is expressed in breast cancer, and agents targeting this pathway have single agent effects (e.g. traztuzumab). Development of resistance may be due to the presence of alternative pathways, particularly activation of the PI3K/Akt/MTOR pathway. We have therefore examined the effect of inhibitors of this pathway (ZSTK474 and sirolimus) in combination with the epidermal growth factor (EGFR) inhibitors erlotinib and gefitinib in breast MCF10a isogenic cell lines with EGFR, BRAF, AKT, and PI3K mutations.

Results: PI3K mutation conferred increased activity of EGFR inhibitors against MCF10a cells in comparison with the parental cell line and other mutations studied. Combination of EGFR inhibitors with either the PI3K inhibitor ZSTK474 or the MTOR inhibitor sirolimus showed increased activity.

Conclusions: These results are encouraging for the use of combinations targeting the PI3K and EGFR pathway simultaneously.

Details

Title
Activity of EGFR, mTOR and PI3K inhibitors in an isogenic breast cell line model
Author
Glaysher, Sharon; Bolton, Louise M; Johnson, Penny; Torrance, Christopher; Cree, Ian A
Pages
397
Publication year
2014
Publication date
2014
Publisher
BioMed Central
e-ISSN
17560500
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/1756-0500-7-397
ProQuest document ID
1542971872
Copyright
© 2014 Glaysher et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.