Cancer

Patient sample and mouse studies suggest inhibiting IL-1α or IL-6 could help treat HER2-positive breast cancer. In patient tumor samples, levels of IL-1α or IL-6 were associated with poor metastasis-free survival, and high tumor levels of IL-1α were associated with high tumor levels of IL-6 or HER2. In a human HER2-positive breast cancer cell line, knockout of IL-1α or IL-6 decreased numbers of cancer stem cells and tumorsphere formation compared with normal IL-1α and IL-6 expression. In a mouse model of HER2-positive breast cancer, systemic knockout of IL-1α decreased tumor growth and metastasis to the lung compared with normal IL-1α expression. In a xenograft mouse model of HER2-positive breast cancer, tumor-specific knockout of IL-1α or IL-6 decreased tumor growth compared with normal IL-1α and IL-6 expression. In an orthotopic xenograft mouse model of HER2-positive breast cancer, a tool compound that inhibits IL-1α signaling plus paclitaxel decreased tumor growth compared with either agent alone. Next steps could include testing IL-1α or IL-6 inhibitors in models of HER2-positive breast cancer.

Johnson & Johnson markets Sylvant siltuximab, a chimeric mAb against IL-6, to treat multicentric Castleman’s disease...