Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified deleted in malignant brain tumors 1, DMBT1, as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed lower levels of DMBT1 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of DMBT1 in primary tumors of the breast, demonstrating decreased expression of a gene defined by its lack of expression in tumors of the brain (5) and whose expression is lacking in multiple human cancers (6-8) as a direct transcriptional result of treatment with trastuzumab.
Functional diffusion map of malignant brain tumors: A surrogate imaging biomarker for early prediction of therapeutic response and patient survival
