Inhibiting BACH1 sensitizes triple-negative breast cancer to metformin
INDICATION: Breast cancer
Patient sample, cell culture and mouse studies suggest BACH1 inhibitors could sensitize triple-negative breast cancer (TNBC) to metformin. In tumor samples from patients with TNBC and basal-like breast cancer, levels of BACH1 mRNA were higher than in other samples from other breast cancer subtypes. In a human TNBC cell line, an siRNA targeting or hemin, an iron-containing porphyrin that inhibits BACH1, increased sensitivity to the oxidative phosphorylation inhibitor metformin compared with a non-targeting shRNA or vehicle, respectively. In two xenograft mouse models of TNBC treated with metformin, co-treatment with the BACH1-targeting shRNA or hemin decreased tumor growth. In a patient-derived xenograft (PDX) mouse model of TNBC, metformin plus hemin decreased tumor growth compared with metformin plus vehicle. Next steps include seeking partners for clinical testing of metformin with undisclosed BACH1 inhibitors...
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