Site Editor
William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Wednesday, February 16, 2022
The stress response protein N-Myc downstream-regulated gene 1 (NDRG1) seems to drive tumor progression and brain metastasis in aggressive breast cancer, according to Bisrat G. Debeb, DVM, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues. The results of this study, which were published in the Journal of the National Cancer Institute, suggested that NDRG1 may serve as a therapeutic target and prognostic biomarker.
The investigators transplanted cells into cleared mammary fat pads or injected them into the tail veins of SCID/beige mice (n = 7–10/group) to examine the role of NDRG1 in tumor growth and brain metastasis in vivo. Using immunohistochemical staining, the investigators assessed patient breast tumors (n = 216) for NDRG1 protein expression.
New sublines that exhibited a distinct propensity to metastasize to the brain were generated from an aggressive breast cancer cell line. In mice, high NDRG1 expression levels seemed to be associated with more prevalent brain metastases (100% vs. 44.4%; P = .01), greater tumor burden, and reduced survival. Silencing NDRG1 appeared to reduce migration, invasion, and tumor-initiating cell subpopulations in aggressive breast cancer cell lines.
Experiments using xenograft models revealed that depleting NDRG1 inhibited primary tumor growth and brain metastasis. In patient breast tumors, NDRG1 expression seemed to be associated with aggressiveness; high expression levels appeared to be associated with shorter durations of overall survival (hazard ratio = 2.27; P = .009) and breast cancer–specific survival (hazard ratio = 2.19; P = .03). The multivariable analysis revealed that NDRG1 may be an independent predictor of overall survival (hazard ratio = 2.17; P = .03) and breast cancer–specific survival (hazard ratio = 2.27; P = .04) rates.
Disclosure: The study authors reported no conflicts of interest.
Journal of the National Cancer Institute
JNCCN Spotlights
