Tamoxifen is a widely used and highly successful drug in the treatment of breast cancer, though resistance to tamoxifen is still a concern in recurrent disease (affecting 25-35% of patients), since therapy resistant metastatic tumor cells are a major cause of death. In a study in this month's Molecular and Cellular Proteomics, researchers have uncovered a protein profile that may accurately predict whether a cancer will be tamoxifen resistant.
Arzu Umar and colleagues in the Netherlands and Washington examined thousands of tumor cells taken from 51 tamoxifen therapy-sensitive and therapy-resistant tumors using a combination of proteomic and mass-spectrometry approaches. Their analysis revealed a set of 100 proteins that were expressed at different abundance levels in the two tumor groups, highlighting a potential profile for tamoxifen resistance.
In addition, they analyzed the most significantly altered protein, called extracellular matrix metalloproteinase inducer, or EMMPRIN, in a separate set 156 breast tumor tissue samples. EMMPRIN levels were higher in tamoxifen-resistant tumors and significantly associated with an earlier tumor progression following first line tamoxifen treatment and poor clinical outcome, suggesting EMMPRIN may be a reliable marker for highly aggressive breast cancer.
While further work with additional samples will be needed to validate these potential markers, the authors note this profile could be clinically useful, especially considering their approach used minute amounts of tissue samples, making it applicable at even the earliest tumor stages.
From the study: "Identification of a Putative Protein Profile Associated with Tamoxifen Therapy Resistance in Breast Cancer" by Arzu Umar, Hyuk Kang, Annemieke Timmermans, Maxime P. Look, Marion E. Meijer-van Gelder, Michael A. den Bakker, Navdeep Jaitly, John W. M. Martens, Theo M. Luider, John A. Foekens and Ljiljana Pa a-Toli
Article Link: http://www.mcponline.org/cgi/content/full/8/6/1278
Corresponding Authors: Arzu Umar, Erasmus Medical Center, Rotterdam, Netherlands; Tel.:31-10-7043814; E-mail: a.umar@erasmusmc.nl
Ljiljana Pasa-Tolic, Pacific Northwest National Laboratory, Richland, Washington; E-mail: Ljiljana.PasaTolic@pnl.gov
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Journal
Molecular & Cellular Proteomics