Tumor-targeting system uses cancer's own mechanisms to betray its location

February 14, 2017 by Liz Ahlberg Touchstone, University of Illinois at Urbana-Champaign
Illinois researchers developed a way to target tumors using sugars that are metabolized by the cancer cell's own enzymes. From left: postdoctoral researcher Yang Liu, professor Jianjun Cheng, postdoctoral researcher Zhiyu Wang, graduate student Kaimin Cai, research scientist Iwona T. Dobrucka, professor Wawrzyniec Lawrence Dobrucki and graduate student Ruibo Wang (seated).Illinois researchers developed a way to target tumors using sugars that are metabolized by the cancer cell's own enzymes. From left: postdoctoral researcher Yang Liu, professor Jianjun Cheng, postdoctoral researcher Zhiyu Wang, graduate student Kaimin Cai, research scientist Iwona T. Dobrucka, professor Wawrzyniec Lawrence Dobrucki and graduate student Ruibo Wang (seated). Credit: Photo by L. Brian Stauffer

By hijacking a cancer cell's own metabolism, researchers have found a way to tag and target elusive cancers with small-molecule sugars. This opens treatment pathways for cancers that are not responsive to conventional targeted antibodies, such as triple-negative breast cancer.

Led by Jianjun Cheng, a Hans Thurnauer Professor of Materials Science and Engineering at the University of Illinois, researchers at Illinois and collaborators in China published their findings in the journal Nature Chemical Biology.

Targeted cancer therapies rely on specific markers on the of . Scientists can design antibodies that seek out those markers and deliver therapeutic or imaging agents. However, some cancers are not eligible for this kind of treatment because they lack surface markers to target.

"For example, we would like to target . This is a deadly , with low survival rates," Cheng said. "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 found a way to mark the cells using a class of small-molecule sugars called azides. Once metabolized in the cell, they are expressed on the surface, and can be targeted by a molecule called DBCO.

"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," Cheng said. "The key question is, how do you put azide just on the tumor?"

To make sure the azide would only be expressed on the surface of cancer cells, the researchers added a protective group to the azide sugar that could only be removed by tumor-specific enzymes. In normal tissues, the azide sugar simply travels through. In tumor cells, it is completely metabolized and expressed on the cell surface, creating specific targets for DBCO to deliver a cargo of cancer-treating drugs or imaging agents.

The researchers tested the azide-based targeting system in mice with tumors from colon cancer, triple-negative breast cancer and .

"We found the tumors had very strong signals compared with other tissues," Cheng said. "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."

Explore further: Study identifies potential targets for treating triple negative breast cancer

More information: Hua Wang et al, Selective in vivo metabolic cell-labeling-mediated cancer targeting, Nature Chemical Biology (2017). DOI: 10.1038/nchembio.2297

Related Stories

Double whammy for triple negative breast cancer

December 5, 2016

A promising new combination therapy for a particularly aggressive form of breast cancer has been identified by Weizmann Institute scientists, as was recently reported in Cancer Research. The potential dual-acting therapeutic ...

Promising findings towards targeted breast cancer therapy

November 14, 2016

New research led by Conway Fellow, Professor Joe Duffy and Professor John Crown in St Vincent's University Hospital has reported for the first time on a new treatment that could be used in the majority of patients with triple ...

Cellular starvation kills treatment-resistant breast cancer

November 21, 2016

Cancer rewires the metabolism of tumor cells, converting them into lean, mean, replicating machines. But like Olympic athletes who rely on special diets to perform, tumor cells' amped-up metabolism can also make them dependent ...

Recommended for you

Plug-and-play technology automates chemical synthesis

September 20, 2018

Designing a new chemical synthesis can be a laborious process with a fair amount of drudgery involved—mixing chemicals, measuring temperatures, analyzing the results, then starting over again if it doesn't work out.

Commercially relevant bismuth-based thin film processing

September 20, 2018

Developing materials suitable for use in optoelectronic devices is currently a very active area of research. The search for materials for use in photoelectric conversion elements has to be carried out in parallel with developing ...

A game of pool in the live cell

September 20, 2018

Cells need to react to environmental changes and maintain a balanced system of signaling cascades within the cell. Proteins outside of the cell, on the cellular surface, inside the cellular membrane, and within the cell orchestrate ...

Nucleation a boon to sustainable nanomanufacturing

September 19, 2018

Calcium carbonate is found nearly everywhere, in sidewalk cement, wall paint, antacid tablets and deep underground. Engineers at Washington University in St. Louis have used a unique set of state-of-the-art imaging techniques ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.