Glycoprotein nonmetastatic B is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer.

Clin Cancer Res 2010 Apr 9;16(7):2147-56. Epub 2010 Mar 9.

Department of Medicine, Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West Montréal, Québec, Canada, H3A 1A3.

Purpose: Although the murine orthologue of glycoprotein nonmetastatic B (GPNMB), Osteoactivin, promotes breast cancer metastasis in an in vivo mouse model, its importance in human breast cancer is unknown. We have examined the significance of GPNMB expression as a prognostic indicator of recurrence and assessed its potential as a novel therapeutic target in breast cancer.

Experimental Design: The clinical significance of GPNMB expression in breast cancer was addressed by analyzing GPNMB levels in several published gene expression data sets and two independent tissue microarrays derived from human breast tumors. GPNMB-expressing human breast cancer cell lines were further used to validate a toxin-conjugated anti-GPNMB antibody as a novel therapeutic agent.

Results: GPNMB expression correlates with shorter recurrence times and reduced overall survival of breast cancer patients. Epithelial-specific GPNMB staining is an independent prognostic indicator for breast cancer recurrence. GPNMB is highly expressed in basal and triple-negative breast cancers and is associated with increased risk of recurrence within this subtype. GPNMB expression confers a more migratory and invasive phenotype on breast cancer cells and sensitizes them to killing by CDX-011 (glembatumumab vedotin), a GPNMB-targeted antibody-drug conjugate.

Conclusions: GPNMB expression is associated with the basal/triple-negative subtype and is a prognostic marker of poor outcome in patients with breast cancer. CDX-011 (glembatumumab vedotin) is a promising new targeted therapy for patients with metastatic triple-negative breast cancers, a patient population that currently lacks targeted-therapy options.

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-09-1611DOI Listing
April 2010

Publication Analysis

Top Keywords

breast cancer
36
gpnmb expression
20
breast
13
novel therapeutic
12
prognostic indicator
12
human breast
12
gpnmb
9
cancer
9
breast cancers
8
triple-negative breast
8
glembatumumab vedotin
8
cdx-011 glembatumumab
8
target breast
8
therapeutic target
8
indicator recurrence
8
glycoprotein nonmetastatic
8
independent prognostic
8
significance gpnmb
8
expression
6
recurrence
5

Similar Publications