Issues

Human epidermal growth factor receptor 2 (HER2 or ErbB2), an ErbB receptor tyrosine kinase, is overexpressed in approximately 20% of cases of human breast cancer, and the ErbB2 signaling pathway is a critical therapeutic target for ErbB2-overexpressing breast cancer. The inhibitory effects of the Gemini vitamin D analogue BXL0124, the synthetic triterpenoid CDDO-Im, and the combination on tumorigenesis in MMTV-ErbB2/neu transgenic mice were investigated. All three treatments repressed the activation of ErbB2, which was prominent at the leading edge of mammary tumors and delayed the development of these tumors without significant toxicity. The cover micrograph (400×) depicts the merged images of activated ErbB2 (pErbB2, shown as green), total ErbB2 (red), and nuclei (blue) in untreated MMTV-ErbB2/neu transgenic mice. Therapeutic efficacy was investigated using the combination of BXL0124 and CDDO-Im. Short-term treatment with the combination did not show effects on tumor growth or the ErbB2 signaling pathway. The present study demonstrates that BXL0124, CDDO-Im, and the combination are potential agents for prevention, but not treatment, of the tumorigenesis of ErbB2-overexpressing breast cancer. See article by So and colleagues (beginning on page 959) for more information.