The interleukin-23 receptor and a subunit for the IL-23 cytokine, IL-23A, are 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 published and public microarray data (3-6) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified the receptor for interleukin-23, IL23R, among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab (3, 4). We also found that the alpha subunit of the IL-23 cytokine, IL23A, was among the genes whose expression changed most significantly in the primary tumors of patients treated with trastuzumab (5, 6). IL23R messenger RNA was expressed at significantly higher levels in the primary tumors of patients treated with trastuzumab than patients not treated with trastuzumab, demonstrating increased expression of the receptor for a cytokine that has been described to promote tumor growth (7) as a transcriptional consequence associated with treatment with trastuzumab.