University researchers develop technology that could provide alternative way to treat cancer

By Emily Scott, Staff writer

For nearly 10 years, University professor Jianjun Cheng had an idea.

He wanted to use click chemistry, a specialized type of chemistry that involves joining substances to biomolecules, which are molecules present in living organisms, in order to target cancer cells. This process is used in targeted cancer therapy, a type of chemotherapy that uses the differences in cancer cells to locate them.

Cheng, a professor of materials science and engineering, led a team of researchers that have developed a way to target cancer cells by taking advantage of the cell’s metabolism.

“This definitely will provide an alternative way to treat cancer,” Cheng said.

Typically, targeted cancer therapies take advantage of antigens, which are toxins present on the surface of cancer cells. These antigens serve as targets that the cell essentially creates itself. Targeted therapies introduce antibodies that counteract with these antigens in order to single out the cancer cells.

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    But some cancers don’t create antigens. So Cheng’s solution was to externally introduce a functional group, a group of atoms or bonds that cause chemical reactions, into the cancer cells.

    This is easy to do in a lab but becomes much more difficult in humans.

    “In a cancer patient, if you don’t even know where the tumor is … how do you recognize those tumors and then put the target there?” Cheng said. “That’s really tricky. So, designing such a technology, that’s the key for this whole process.”

    Cheng thought to take advantage of a cell’s metabolism, a process that involves the cell processing sugar to provide energy for cell functions. When this happens, the sugar breaks apart and goes to the surface of the cell.

    Cheng and his team came up with the idea to design a specialized sugar that could be introduced to the tumor, undergo metabolism, break apart and reach the surface, and thus become a target.

    But they had to design a sugar that would only metabolize in cancer cells, and not in normal cells.

    They used the functional group azide, a small-molecule sugar. To ensure this sugar would only metabolize in cancer cells, they had to introduce something else.

    “This is the really tricky part,” Cheng said. “What we did is we put a protecting group here. This protecting group inhibits the sugar activity, unless it is removed.”

    The other way it can be removed is by a tumor-specific enzyme. When the enzyme removes the sugar, the sugar can then be metabolized. However, this wouldn’t happen in other cells.

    Once the sugar becomes metabolized, it goes to the cell surface and can then be targeted by therapeutic drugs.

    These findings were recently published in the journal Nature Chemical Biology. The technology they developed is the first of its kind and could become useful in treating cancers that don’t express antigens. Because they don’t express antigens, these cancers can’t be treated by current targeted cancer therapies.

    An example of a cancer that doesn’t express antigens is triple-negative breast cancer, an aggressive cancer that can be difficult to treat. They also tested their technology on colon and lung cancer.

    “I think many cancers can potentially be utilized for this treatment because this is a very practical technology,” Cheng said. “Any cancer, if we can identify specific enzymes that can create this bond and activate to the sugar, can potentially be utilized for treatment. It’s really depending on how many different types of enzymes we can identify for the specific tumor.”

    Cheng said this technology could also compete with the current targeted cancer therapies. However, it could still be several years before it’s transformed into a treatment that’s available for cancer patients.

    The team is currently in the beginning steps of licensing the technology. They’ve started a company at the University’s Research Park that they will use to develop the technology further.

    Kaimin Cai, a University Ph.D. student who has been involved with this research for over two years, is leading the team’s efforts in transitioning from research to market.

    He said they are currently working on developing a “next generation” sugar that could perform better than the sugar they originally tested. Additionally, they are exploring other drugs they could use with this technology and other cancers this technology could help treat.

    Cai said it’s exciting to be a part of research that could benefit future cancer treatment.

    “Usually we work in the lab, do something, publish a paper and no one really cares,” Cai said. “It’s really exciting to find something that has the potential to be used to the advantage of society.”