A chimeric SERM-histone deacetylase inhibitor approach to breast cancer therapy.

ABSTRACT: Breast cancer remains a significant cause of death in women, and few therapeutic options exist for estrogen receptor negative (ER (-)) cancers. Epigenetic reactivation of target genes using histone deacetylase (HDAC) inhibitors has been proposed in ER (-) cancers to resensitize to therapy using selective estrogen receptor modulators (SERMs) that are effective in ER (+) cancer treatment. Based upon preliminary studies in ER (+) and ER (-) breast cancer cells treated with combinations of HDAC inhibitors and SERMs, hybrid drugs, termed SERMostats, were designed with computational guidance. Assay for inhibition of four type I HDAC isoforms and antagonism of estrogenic activity in two cell lines yielded a SERMostat with 1-3 μM potency across all targets. The superior hybrid caused significant c

SUBMITTER: Patel HK 

PROVIDER: S-EPMC3962780 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature