Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer.

ABSTRACT: Resistance to the selective estrogen receptor modulator tamoxifen and to aromatase inhibitors that lower circulating estradiol occurs in up to 50% of patients, generally leading to an endocrine-independent ER+ phenotype. Selective ER downregulators (SERDs) are able to ablate ER and thus, theoretically, to prevent survival of both endocrine-dependent and -independent ER+ tumors. The clinical SERD fulvestrant is hampered by intramuscular administration and undesirable pharmacokinetics. Novel SERDs were designed using the 6-OH-benzothiophene (BT) scaffold common to arzoxifene and raloxifene. Treatment-resistant (TR) ER+ cell lines (MCF-7:5C and MCF-7:TAM1) were used for optimization, followed by validation in the parent endocrine-dependent cell line (MCF-7:WS8), in 2D and 3D cultures, using E

SUBMITTER: Xiong R 

PROVIDER: S-EPMC5786431 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature