HonCode

Go Back   HER2 Support Group Forums > Articles of Interest
Register Gallery FAQ Members List Calendar Search Today's Posts Mark Forums Read

Reply
 
Thread Tools Display Modes
Old 11-09-2013, 09:02 PM   #1
'lizbeth
Senior Member
 
'lizbeth's Avatar
 
Join Date: Apr 2008
Location: Sunny San Diego
Posts: 2,214
Post Neuregulin autocrine signaling promotes self-renewal of breast tumor-initiating cells

Cancer Res. 2013 Oct 31. [Epub ahead of print]
Neuregulin autocrine signaling promotes self-renewal of breast tumor-initiating cells by triggering HER2/HER3 activation.

Lee CY, Lin Y, Bratman S, Feng W, Kuo A, Scheeren F, Engreitz JM, Varma S, West R, Diehn M.
Source

Stanford Cancer Institute/Stem Cell Institute, Stanford University.

Abstract

Currently only patients with HER2-positive tumors are candidates for HER2-targeted therapies. However, recent clinical observations suggest that the survival of patients with HER2-low breast cancers, who lack HER2 amplification, may benefit from adjuvant therapy that targets HER2. In this study, we explored a mechanism through which these benefits may be obtained. Prompted by the hypothesis that HER2/HER3 signaling in breast tumor-initiating cells (TICs) promotes self-renewal and survival, we obtained evidence that neuregulin 1 (NRG1) produced by TICs promotes their proliferation and self-renewal in HER2-low tumors, including in triple-negative breast tumors. Pharmacologic inhibition of EGFR, HER2 or both receptors reduced breast TIC survival and self-renewal in vitro and in vivo and increased TIC sensitivity to ionizing radiation. Through a tissue microarray analysis, we found that NRG1 expression and associated HER2 activation occurred in a subset of HER2-low breast cancers. Our results offer an explanation for why HER2 inhibition blocks the growth of HER2-low breast tumors. Moreover, they argue that dual inhibition of EGFR and HER2 may offer a useful therapeutic strategy to target TICs in these tumors. In generating a mechanistic rationale to apply HER2 targeting therapies in patients with HER2-low tumors, this work shows why these therapies could benefit a considerably larger number of breast cancer patients than they currently reach.
'lizbeth is offline   Reply With Quote
Reply

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is On

Forum Jump


All times are GMT -7. The time now is 02:28 AM.


Powered by vBulletin® Version 3.8.7
Copyright ©2000 - 2024, vBulletin Solutions, Inc.
Copyright HER2 Support Group 2007 - 2021
free webpage hit counter