Therapeutics: X-box binding protein 1 (XBP1)
Mouse studies suggest inhibiting XBP1 could help treat ovarian cancer. In ovarian cancer patients and a mouse model of the disease, levels of XBP1 transcripts were higher in tumor-infiltrating dendritic cells (DCs) than in non-tumor-infiltrating DCs. In mouse models of primary and metastatic ovarian cancer, DC-specific knockdown of XBP1 decreased tumor growth and metastasis and increased survival compared with normal XBP1 expression. In the metastatic ovarian cancer model, nanoparticles loaded with siRNA against XBP1 decreased the number of metastatic cancer cells in the peritoneum and levels of malignant ascites, and increased survival compared with nanoparticles loaded with control siRNA. Next steps include testing XBP1 inhibition in additional cancer models and in combination with cancer immunotherapies. ...