Seviteronel plus chemotherapy is a new targeted combination therapy to treat triple-negative breast cancer

Therapeutic strategies that improve survival outcomes for advanced-stage breast cancers have proven a major clinical challenge. Here, we define an androgen receptor signalling network that governs the maintenance and de novo formation of cancer stem cells in triple-negative breast cancer. In response to chemotherapy, androgen receptor activation switches cells into a cancer stem cell state, while androgen receptor antagonism suppresses cancer stem cell formation and function. In vivo, we validate that the androgen receptor antagonist, seviteronel, significantly improves chemotherapy-mediated inhibition of primary and metastatic tumour growth. HCC38 cells were purchased from ATCC and cultured in RPMI containing 10% FBS containing penicillin/streptomycin (PS; 5.000 units penicillin and 5 mg streptomycin/ml in H2O, Sigma Aldrich, cat no. P4333). All cell lines were routinely tested to confirm the absence of mycoplasma contamination. HCC38 CD44Hi cells treated with control siRNA or two different siRNAs targeting AR (AR ex1, AR ex7). HCC38 CD44Hi cells also followed treatment with AR antagonists vehicle (DMSO), Seviteronel, Abiraterone or Enzalutamide.