title: Resistance to HER2-targeted therapies: a potential role for FOXM1.
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.
authors.affiliation: Molecular & Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University.
authors.forename: Bridgette F
authors.initials: BF
authors.lastname: Peake
authors.affiliation: Molecular & Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University ; Cancer Biology Program, Graduate Division of Biological and Biomedical Sciences, Emory University ; Department of Pharmacology, Emory University ; Department of Hematology and Medical Oncology, Emory University ; Winship Cancer Institute, Emory University.
authors.forename: Rita
authors.initials: R
authors.lastname: Nahta
keywords: breast cancer; foxm1; her2; lapatinib; resistance; trastuzumab