BioCentury
ARTICLE | Distillery Therapeutics

Cancer

May 9, 2018 3:22 PM UTC

Patient sample and cell culture studies suggest inhibiting BARD1, BRCA1, CDK1 or CKD12 could help treat tamoxifen-resistant breast cancer. In tumor tissue from 27 recurrent breast cancer patients whose tumors became resistant to tamoxifen, BARD1 and BRCA1 expression was higher in relapsed tumors than in matched primary tumors. In two tamoxifen-resistant human breast cancer cell lines, siRNA targeting BARD1 or BRCA1 combined with the generic chemotherapy cisplatin or doxorubicin decreased proliferation compared with chemotherapy alone. In one of the cell lines, siRNA targeting CDK1 or CDK12 plus cisplatin increased apoptosis compared with cisplatin alone, and in both cell lines, the dual CDK1/CDK12 inhibitor dinaciclib plus cisplatin decreased proliferation. Next steps could include identifying and testing BRCA1 or BARD1 inhibitors in mouse models of tamoxifen-resistant breast cancer...