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

Fasenra (benralizumab) receives US FDA approval fo…

AstraZeneca and its global biologics research and development arm, MedImmune, announced that the US Food and Drug Administration (FDA) has approved Fasenra (benralizumab)...

Alzheimer's disease might be a 'whole body' proble…

Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain. But research from the University of British Columbia and Chinese scie...

Cancer cells destroyed with dinosaur extinction me…

Cancer cells can be targeted and destroyed with the metal from the asteroid that caused the extinction of the dinosaurs, according to new research by an international col...

Novartis confirms leadership in multiple sclerosis…

Novartis today announced it will present 54 scientific abstracts from across its multiple sclerosis (MS) research portfolio at the 7th Joint European and Americas Committ...

Amgen and Novartis announce expanded collaboration…

Amgen (NASDAQ:AMGN) and Novartis announced an expanded collaboration with the Banner Alzheimer's Institute (BAI) to initiate a new trial - the Alzheimer's Prevention Init...

Transplanted hematopoietic stem cells reverse dama…

Researchers at University of California San Diego School of Medicine report that a single infusion of wildtype hematopoietic stem and progenitor cells (HSPCs) into a mous...

Pfizer receives FDA approval for SUTENT® (sunitini…

Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug Administration has approved a new indication expanding the use of SUTENT® (sunitinib malate) to include...

Novartis announces the planned acquisition of Adva…

Novartis announced today, that it has entered a memorandum of understanding with Advanced Accelerator Applications (AAA) under which Novartis intends to commence a tender...

'Precision Medicine' may not always be so precise

Precision Medicine in oncology, where genetic testing is used to determine the best drugs to treat cancer patients, is not always so precise when applied to some of the w...

New tissue-engineered blood vessel replacements on…

Researchers at the University of Minnesota have created a new lab-grown blood vessel replacement that is composed completely of biological materials, but surprisingly doe...

China's out of control 'silent killer' affects one…

More than one-third of adults in China have high blood pressure - often dubbed the "silent killer" for its lack of symptoms - but only about one in 20 have the condition ...

New US study reveals key reasons why millions of p…

Few of the more than 90 million Americans(1) with obesity are seeking and receiving long-term obesity care, according to new data from the Awareness, Care and Treatment I...

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 ]