Therapeutics: MicroRNA-551b (miR-551b); signal transducer and activator of transcription 3 (STAT3)
Patient sample, cell culture and mouse studies suggest inhibiting miR-551b or STAT3 could help treat serous ovarian cancer. In patients with high-grade serous ovarian cancer, miR-551b levels were higher in ovarian tumor samples than in normal ovarian tissue, and high tumor levels of miR-551b or STAT3 correlated with poor survival. In two human ovarian cancer cell lines overexpressing miR-551b, an oligonucleotide targeting miR-551b decreased STAT3 levels and spheroid growth compared with a control oligo, and shRNA targeting STAT3 decreased proliferation and spheroid formation compared with scrambled shRNA. In a xenograft mouse model of ovarian cancer, the oligo targeting miR-551b decreased tumor number and growth compared with the control oligo. Next steps could include testing STAT3 inhibitors in models of serous ovarian cancer.
Ionis Pharmaceuticals Inc. and AstraZeneca plc have AZD9150 (IONIS-STAT3RX), an antisense inhibitor of STAT3, in Phase I/II testing to treat advanced cancer, B cell lymphoma, lymphoma and liver cancer and Phase I testing to treat hematologic malignancies. ...