Resistance to HER2-targeted therapies: a potential role for FOXM1.

• Type of Material: Article
• Authors: Bridgette F. Peake, Emory University; Rita Nahta, Emory University
• Language: English
• Date: 2014
• Publisher: Future Medicine: Open Access Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Future Medicine Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.2217/bmt.14.33
• Title of Journal or Parent Work: Breast Cancer Management
• ISSN: 1758-1923
• Volume: 3
• Issue: 5
• Start Page: 423
• End Page: 431
• Grant/Funding Information: Bridgette Peake acknowledges funding from the Molecular Systems and Pharmacology Training Grant at Emory University (5T32GM0080602-17).; We acknowledge Winship Cancer Institute P30 CA138292.; Rita Nahta acknowledges funding from NIH R01CA157754 and is a Glenn Breast Cancer Research Scholar at the Winship Cancer Institute of Emory University.
• Keywords: foxm1; resistance; her2; lapatinib; breast cancer; trastuzumab
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Despite the tremendous efficacy of trastuzumab against HER2-overexpressing metastatic breast cancers, a significant fraction of women demonstrate progressive disease during treatment. Multiple mechanisms have been proposed to mediate trastuzumab resistance. In this mini-review, we discuss the evidence supporting FOXM1 as a mediator of resistance and potential new therapeutic target in trastuzumab-refractory breast cancer. FOXM1 expression is significantly elevated in multiple breast cancer data sets. Some studies suggest a direct correlation between FOXM1 and HER2 expression levels. In addition, overexpression of FOXM1 reduces the sensitivity of HER2-positive breast cancer cells to trastuzumab or lapatinib. Conversely, knockdown or pharmacological inhibition of FOXM1 rescues resistance to HER2-targeted therapies. Current pre-clinical information supports further investigation of the role of FOXM1 in trastuzumab-resistant breast cancer.