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

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 surface of cancer cells. 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 triple-negative breast cancer. This is a deadly breast cancer, 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 metastatic breast cancer.

"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."

Wang H, Wang R, Cai K, He H, Liu Y, Yen J, Wang Z, Xu M, Sun Y, Zhou X, Yin Q, Tang L, Dobrucki IT, Dobrucki LW, Chaney EJ, Boppart SA, Fan TM, Lezmi S, Chen X, Yin L, Cheng J.
Selective in vivo metabolic cell-labeling-mediated cancer targeting.
Nat Chem Biol. 2017 Feb 13. doi: 10.1038/nchembio.2297.

Most Popular Now

Novartis confirms 5 year data for first and only f…

Novartis, a global leader in Immunology & Dermatology, confirmed today positive 5 year efficacy and safety results for Cosentyx® from a Phase III long-term extension stud...

FDA approves Rituxan Hycela (rituximab and hyaluro…

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the US Food and Drug Administration (FDA) approved Rituxan Hycela™ (rituximab and hyaluronidase human) for subcuta...

Merck Foundation established

Merck, a leading science and technology company, today announced the establishment of the Merck Foundation. Through this foundation Merck combines many of its corporate r...

Researchers develop microneedle patch for flu vacc…

A National Institutes of Health-funded study led by a team at the Georgia Institute of Technology and Emory University has shown that an influenza vaccine can produce rob...

Novartis Phase III study shows ACZ885 (canakinumab…

Novartis today announced topline results from the global Phase III CANTOS study investigating the efficacy, safety and tolerability of ACZ885 (canakinumab) in combination...

Jardiance® (empagliflozin) analysis reinforces est…

An analysis of pooled safety data from 15 studies plus 4 extension studies involving more than 12,500 adults with type 2 diabetes demonstrated treatment with Jardiance® (...

Systems pharmacology modelers accelerate drug disc…

Alzheimer's is a chronic neurodegenerative disease which leads to the senile cognitive impairment and memory loss. Every third person older than 70 years suffers from it...

Does the emperor have clothes?

Discovered more than two decades ago, the hormone leptin has been widely hailed as the key regulator of leanness. Yet, the pivotal experiments that probe the function of ...

Alzheimer's and Parkinson's spurred by same enzyme

Alzheimer's disease and Parkinson's disease are not the same. They affect different regions of the brain and have distinct genetic and environmental risk factors. But at ...

Merck awards €1.25 million to research projects th…

Merck, a leading science and technology company, today announced its commitment to award €1.25 million to research projects in the field of fertility, supporting the adva...

Trials show unique stem cells a potential asthma t…

A study led by scientists at Monash University has shown that a new therapy developed through stem cell technology holds promise as a treatment for chronic asthma. The Mo...

Researchers publish new findings on influence of h…

Poor diet is associated with 80% of colorectal cancer cases, but the exact pathways by which diet leads to cancer are not known. In a newly published study, Cleveland Cli...

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]