Researchers have discovered a way to tag cancer cells of tumors that are difficult to target because they lack suitable receptors. The team — including scientists from the University of Illinois at Urbana-Champaign and research centers in China — suggest that their approach, which they tested in mice, could lead to new targeted therapies for cancers that do not respond to those currently available, such as triple-negative breast cancer.
Study leader Jianjun Cheng, a professor of materials science and engineering at Illinois, said metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto the cell surface; however, cancer-selective labeling still remains a great challenge.
The team reports the design of sugars that can selectively label cancer cells both in vitro and in vivo. Specifically, they inhibited the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells. 
Targeted cancer therapy aims to single out only cancer cells and leave healthy cells intact. In order to do this, researchers must find features that distinguish the tumor cells of particular cancer from healthy cells, so that the treatment can target those features specifically.
One feature that can differentiate cancer cells from healthy cells is the cell surface receptor, a type of molecule that protrudes on the outside of the cell and acts as a conduit for signals between the cell and its environment said Catharine Paddock, PhD, in Medical News Today. 
Scientists can devise antibodies that seek out the receptors that are specific to cancer cells in order to deliver targeted drugs or imaging agents.
However, some cancers are notoriously difficult to distinguish in this way because they lack suitable surface receptors.
One such cancer is triple-negative breast cancer. Tumor cells of this type of cancer lack the three most common types of the receptor known to drive most breast cancer growth: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2).
“It's very much like a key in a lock. They are very specific to each other,” Prof. Cheng said. “DBCO and azide react with each other with high specificity. We call it click chemistry. The key question is, how do you put azide just on the tumor?
“For the first time, we labeled and targeted tumors with small molecule sugars in vivo, and we used the cancer cell's own internal mechanisms to do it.”