Arachidonate 12-lipoxygenase (ALOX12) is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.
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 public microarray data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified arachidonate 12-lipoxygenase, encoded by ALOX12, 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 higher levels of ALOX12 messenger RNA than did patients not treated with trastuzumab, demonstrating that in patients with breast cancer, administration of trastuzumab is associated with increased expression of an enzyme (5) whose inhibition results in enhanced responsiveness of breast cancer cells to chemotherapeutics in vitro (6).