{"title":"Resistance to HER2-targeted therapies: a potential role for FOXM1.","authors":"Bridgette F Peake, Rita Nahta","doi":"10.2217/bmt.14.33","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":43086,"journal":{"name":"Breast Cancer Management","volume":"3 5","pages":"423-431"},"PeriodicalIF":0.4000,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/bmt.14.33","citationCount":"16","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Management","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2217/bmt.14.33","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 16
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.
期刊介绍：
Breast Cancer Management (ISSN: 1758-1923) addresses key issues in disease management by exploring the best patient-centered clinical research and presenting this information both directly, as clinical findings, and in practice-oriented formats of direct relevance in the clinic. The journal also highlights significant advances in basic and translational research, and places them in context for future therapy. Breast Cancer Management provides oncologists and other health professionals with the latest findings and opinions on reducing the burden of this widespread disease. Recent research findings and advances clinical practice in the field are reported and analyzed by international experts. The journal presents this information in clear, accessible formats. All articles are subject to independent review by a minimum of three independent experts. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal’s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3. Coverage includes: Diagnosis and imaging, Surgical approaches, Radiotherapy, Systemic therapies, Cancer clinical trials, Genetic aspects of disease, Personalized medicine, Translational research and biomarker studies, Management of psychological distress, Epidemiological studies, Pharmacoeconomics, Evidence-based treatment guidelines.
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