Proteomics

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Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

ABSTRACT: Human breast cancer cell lines were cultured in phenol red-free RPMI1640 medium supplemented with 10% fetal bovine serum and 1nM E2. All cell lines were banked in multiple aliquots to reduce the risk of phenotypic drift and identity confirmed using STR. Cells were routinely screened for mycoplasma contamination. Long-term E deprived (LTED) cells modelling resistance to an AI were derived from all parental cell lines as previously described. Two models of MCF7-LTED cells were available: one harbouring a Y537C mutation in ESR1 and the other with wt-ESR1. SUM44-LTED was shown to harbour a natural heterozygous ESR1Y537S mutation. Elacestrant resistant cell lines were generated by growing parental cells (MCF7-LTEDY537C) long-term in the presence of RPMI1640 containing 10% DCC + 0.1nM E2 + 1μM elacestrant. All cell lines were stripped of steroids for 48-72 hours prior to the start of experiments.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Nikiana Simigdala  

LAB HEAD: Lesley-Ann Martin

PROVIDER: PXD031377 | Pride | 2023-03-10

REPOSITORIES: Pride

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Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen-receptor positive endocrine-resistant and fulvestrant-resistant breast cancer.

Pancholi Sunil S   Simigdala Nikiana N   Ribas Ricardo R   Schuster Eugene E   Leal Mariana Ferreira MF   Nikitorowicz-Buniak Joanna J   Rega Camilla C   Bihani Teeru T   Patel Hitisha H   Johnston Stephen R SR   Dowsett Mitch M   Martin Lesley-Ann LA  

NPJ breast cancer 20221129 1

The selective oestrogen receptor (ER) degrader (SERD), fulvestrant, is limited in its use for the treatment of breast cancer (BC) by its poor oral bioavailability. Comparison of the orally bioavailable investigational SERD elacestrant, versus fulvestrant, demonstrates both drugs impact tumour growth of ER+ patient-derived xenograft models harbouring several ESR1 mutations but that elacestrant is active after acquired resistance to fulvestrant. In cell line models of endocrine sensitive and resis  ...[more]

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