A novel biomarker and therapeutic target for chemo-resistant triple negative breast cancer
Breast cancer is among the most prevalent cancers, affecting roughly 1 in 8 women. Consequently, the economic burden for breast cancer is proportionally high, costing over $80 billion per year, globally. Triple negative breast cancer (TNBC) makes up 15-20% of all diagnosed cases and is typically more aggressive and difficult to treat than other forms of breast cancer. Current treatment options for TNBC include gross tumor resection, to remove the majority of the tumor burden, and chemotherapy, to help eliminate the residual infiltrating tumor cells. However, while most patients with TNBC initially respond to chemotherapy, chemo-resistant cells often persist and go on to repopulate a new tumor, which accounts for the high mortality rate of this disease. Thus, the primary challenge in the field of TNBC treatments is identifying novel molecular biomarkers on chemo-resistant breast cancer cells that can also serve as therapeutic targets.
Dr. Bachelder and colleagues have recently demonstrated that chemo-resistant TNBC cells exhibit a marked increase in the surface expression of precursor N-cadherin, or pro-N-cadherin, compared to chemo-sensitive TNBC cells. Furthermore, surface pro-N-cadherin was shown to be associated with an elevated invasive potential of TNBC cells, as well as multi-drug resistance. In accordance with their in vitro findings, surface pro-N-cadherin was shown to be dramatically increased in TNBC biopsies following chemotherapy compared to matched samples evaluated prior to chemotherapy. These results implicate surface pro-N-cadherin not only as a biomarker for chemo-resistant TNBC cells but also as a potential therapeutic target.
Pro-N-cadherin represents a promising therapeutic target due to its 1) preferential expression on chemo-resistant TNBC cells and 2) apparent function in TNBC invasion.