Deciphering the Role of Insulin-Like Growth Factor-I Receptor in Trastuzumab Resistance

• Type of Material: Article
• Authors: Rita Nahta, Emory University
• Language: English
• Date: 2012
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Rita Nahta.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1155%2F2012%2F648965
• Title of Journal or Parent Work: Chemotherapy Research and Practice
• Volume: 2012
• Grant/Funding Information: National Cancer Institute (K01CA118174 and 3K01CA118174-5S1), Georgia Cancer Coalition Distinguished Cancer Scholar Award, P30 CA138292 (Winship Cancer Institute).
• Research Categories: Health Sciences, Pharmacology

Abstract

Resistance to the HER2-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-overexpressing metastatic breast cancer. Increased expression or signaling of the insulin-like growth factor-I receptor (IGF-IR) has been reported in a subset of cell lines and clinical samples derived from trastuzumab-resistant breast cancers. Genetic and pharmacologic inhibition of IGF-IR signaling has been shown to improve response to trastuzumab in trastuzumab-naïve and trastuzumab-resistant models. In this paper, we will discuss the role of IGF-IR signaling in trastuzumab resistance. Further, we will discuss cotargeting IGF-IR and HER2 as a potential therapeutic strategy for HER2-over-expressing breast cancers that have progressed on trastuzumab treatment.