Authors: Jade Parker, Future Science Group
In a study published recently in Nature Chemical Biology, a multi-institutional group of researchers have uncovered a novel method of selectively labelling cancer cells both in vitro and in vivo.
Being able to distinguish cancer cells from normal cells is vital for cancer diagnosis and targeted therapy. In this study, researcher’s metabolically glycoengineered unnatural sugars in order to manually introduce chemical receptors onto the surface of normal and cancer cells. They then went on to target these receptors with a molecule termed DBCO.
Lead author Jianjun Cheng from the University of Illinois (IL, USA) explained: “It’s very much like a key in a lock. They are very specific to each other. DBCO and azide react with each other with high specificity. We call it click chemistry.”
The researchers believe their method may help uncover novel treatment regimens for cancers such as triple-negative breast cancer, which are not responsive to conventional targeted antibody treatments.
Cheng continued: “…We would like to target triple-negative breast cancer. This is a deadly breast cancer, with low survival rates. We don’t have any targeted therapeutics so far, because it doesn’t have any of the receptors on it that we normally target. Our question was, can we create an artificial receptor?”
The researchers added a protective group to the azide sugar that could only be removed by tumor-specific enzymes to ensure the azide would solely be expressed on the surface of cancer cells, creating a specific target for DBCO. The team tested their azide-based targeting system in mice with tumors from metastatic breast cancer, colon cancer and triple-negative breast cancer.
“We found the tumors had very strong signals compared with other tissues. 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,” Cheng concluded.
Wang H, Wang R, Cai K et al. Selective in vivo metabolic cell-labeling-mediated cancer targeting doi:10.1038/nchembio.2297 (2016); Illinois news bureau press release https://news.illinois.edu/blog/view/6367/463257