The radiosensitizing effects of monopolar spindle kinase I in syngeneic models of triple negative breast cancer and its implications on the tumor immune microenvironment

Abstract Triple negative breast cancer (TNBC) is an aggressive subset with poor outcomes. TNBCs do not express the estrogen, progesterone, or HER2 receptors and are thus candidates for antiestrogen anti-HER2 therapies, leaving few effective treatments. One therapeutic strategy to target molecular components of individual patient’s cancer. Prior work in our group has nominated monopolar spindle kinase I (TTK) as a gene that upregulated cancerous tissue compared healthy correlates locoregional recurrence following radiation patients. However, effects TTK inhibition on immune system understood. We hypothesize inhibitor empesertib radiosensitizes murine TNBC models vitro vivo modulates tumor microenvironment. Single agent inhibited growth cells IC 50values up 30nM. Sub-IC radiosensitized 4T1 (radiation enhancement ratio rER: 2.4 ± 0.4) Py8119 (rER: 1.5 0.1) cells. knockdown (via shRNA) also resulted changes radiosensitization vitro. Furthermore, we observed similar phenotype vivo. In model, mice receiving combined treatment had decreased single-agent therapies vehicle (****p<0.0001). Quantities monocyte derived suppressor were altered inhibition. This therapy suggests underlying mechanisms due important TNBC. Future will examine systemic tumoral changes.