BioCentury
ARTICLE | Distillery Therapeutics

Cancer

November 9, 2016 9:05 PM UTC

Patient sample, cell culture and mouse studies suggest inhibiting neutrophil extracellular traps (NETs) with DNASE1 or other agents could help treat metastatic breast cancer. In primary tumor samples from 20 patients with metastatic breast cancer, the number of NETs was higher in triple-negative breast cancer (TNBC) tumors than in less aggressive luminal breast tumors, and NETs were detected in 16 of 20 primary tumors and 13 of 19 metastatic tumors. In a human breast cancer cell line co-cultured with neutrophils, the NET-digesting enzyme DNASE1 decreased cancer cell invasiveness compared with vehicle. In a mouse mammary cancer cell line co-cultured with neutrophils, DNASE1 decreased cancer cell migration. In a human breast cancer cell line, sivelestat or an NADPH oxidase inhibitor tool compound, which both block NET formation, decreased invasiveness. In a mouse model of breast cancer, DNASE1-coated nanoparticles decreased metastasis to the lung compared with uncoated nanoparticles. Next steps include testing the efficacy of various NET targeting approaches in cell culture and animal models...