Cancer

Cell culture and mouse studies identified benzothiophene-based selective estrogen receptor down-regulators (SERDs) that could help treat drug-resistant breast cancers. Chemical synthesis and testing in cell-based assays of 6-OH-benzothiophene analogs identified six compounds that down-regulated ESR1 with IC₅₀ values of 0.7-1.1 nM and inhibited survival of tamoxifen- and aromatase inhibitor-resistant breast cancer cell lines with IC₅₀ values of 0.3-1.3 nM. In one of the tamoxifen-resistant cell lines, one compound decreased spheroid growth compared with the SERD ARN-810. In a xenograft mouse model of tamoxifen-resistant breast cancer, two of the compounds decreased tumor growth compared with vehicle. Next steps could include testing the SERDs in models of aromatase inhibitor-resistant breast cancer.

The Genentech Inc. unit of Roche has ARN-810 (GDC-0810; RG6046), an oral SERD, in Phase II testing for estrogen receptor-positive breast cancer...