Table of Contents
Chemotherapy Research and Practice
Volume 2012, Article ID 648965, 7 pages
Review Article

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

Departments of Pharmacology, Hematology and Medical Oncology, School of Medicine; Winship Cancer Institute; Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Suite 5001, 1510 Clifton Road, Atlanta, GA 30322, USA

Received 25 April 2012; Accepted 19 June 2012

Academic Editor: Sue S. Yom

Copyright © 2012 Rita Nahta. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.