Navigation Links
New enzyme targets for selective cancer therapies

(Edmonton) Thanks to important discoveries in basic and clinical research and technological advances, the fight against cancer has mobilized into a complex offensive spanning multiple fronts.

Work happening in a University of Alberta chemistry lab could help find new and more selective therapies for cancer. Researchers have developed a compound that targets a specific enzyme overexpressed in certain cancersand they have tested its activity in cells from brain tumours.

Chemistry professor Christopher Cairo and his team synthesized a first-of-its-kind inhibitor that prevents the activity of an enzyme called neuraminidase. Although flu viruses use enzymes with the same mechanism as part of the process of infection, human cells use their own forms of the enzyme in many biological processes.

Cairo's group collaborated with a group in Milan, Italy, that has shown that neuraminidases are found in excess amounts in glioblastoma cells, a form of brain cancer.

In a new study, a team from the National Cancer Institute tested Cairo's enzyme inhibitor and found that it turned glioblastoma cancer stem cellsfound within a tumour and believed to drive cancer growthinto normal cells. The compound also caused the cells to stop growing, suggesting that this mechanism could be important for therapeutics. Results of their efforts were published Aug. 22 in the Nature journal Cell Death & Disease.

Cairo said these findings establish that an inhibitor of this enzyme could work therapeutically and should open the door for future research.

"This is the first proof-of-concept showing a selective neuraminidase inhibitor can have a real effect in human cancer cells," he said. "It isn't a drug yet, but it establishes a new target that we think can be used for creating new, more selective drugs."

Long road from proof of concept to drug

Proving the compound can successfully inhibit the neuraminidase enzyme in cancer cells is just the first step in determining its potential as a therapy.

In its current form, the compound could not be used as a drug, Cairo explained, largely because it wasn't designed to breach the blood-brain barrier making it difficult to reach the target cells. The team in Milan had to use the compound in very high concentrations, he added.

The research advances our understanding of how important carbohydrates are to the function of cells. Although most of us think of glucose (blood sugar) as the only important sugar in biology, there is an entire area of research known as glycobiology that seeks to understand the function of complex carbohydrate structures in cells. Carbohydrate structures cover the surface of cells, and affect how cells interact with each other and with pathogens.

Scientists have known for decades that the carbohydrates found on cancer cells are very different from those on normal cells. For example, many cancers have different amounts of specific residues like sialic acid, or may have different arrangements of the same residues.

"The carbohydrates on the cell surface determine how it interacts with other cells, which makes them important in cancer and other diseases. So, if we can design compounds that change these structures in a defined way, we can affect those interactions," Cairo explained. "Finding new enzyme targets is essential to that process, and our work shows that we can selectively target this neuraminidase enzyme."

Although there has been a lot of work on targeting viral neuraminidase enzymes, Cairo's team has found inhibitors of the human enzymes. "The challenge in human cells is that there are four different isoenzymes. While we might want to target one for its role in cancer, hitting the wrong one could have harmful side-effects," he said.

The U of A team reached out to their colleagues in Milan who were studying the role of a specific neuraminidase isoenzyme in cancer cells isolated from patients. Cairo approached them about testing a compound his team identified last year, which was selective for the same isoenzyme.

"I expected it would do something, but I didn't know it would be that striking. It came out beautifully," Cairo said.

The U of A team is already working on improving the compound, and developing and testing new and existing inhibitors using a panel of in vitro assays they developed.

"We've been working on these enzymes for about five years. Validation of our strategydesign of a selective neuraminidase inhibitor and application in a cell that overexpresses that enzymeis an achievement for us."


Contact: Bryan Alary
University of Alberta

Related biology news :

1. Penn biologists identify a key enzyme involved in protecting nerves from degeneration
2. New immune defense enzyme discovered
3. Genzyme/ACMG Foundation Genetics Training Award in Clinical Biochemical Genetics announced
4. ORNL process improves catalytic rate of enzymes by 3,000 percent
5. Scientists discover enzyme that could slow part of the aging process in astronauts -- and the elderly
6. New screening technique yields elusive compounds to block immune-regulating enzyme
7. UCLA scientists discover how key enzyme involved in aging, cancer assembles
8. Is it a rock, or is it Jell-O? Defining the architecture of rhomboid enzymes
9. Brain enzyme is double whammy for Alzheimers disease
10. Ancient enzymes function like nanopistons to unwind RNA
11. Remarkable enzyme points the way to reducing nitric acid use in industry
Post Your Comments:
Related Image:
New enzyme targets for selective cancer therapies
(Date:11/2/2015)...  SRI International has been awarded a contract of ... to the National Cancer Institute (NCI) PREVENT Cancer Program ... modern testing and support facilities, and analytical instrumentation to ... studies to evaluate potential cancer prevention drugs. ... Drug Development Program is an NCI-supported pipeline to bring ...
(Date:10/29/2015)... 29, 2015  Rubicon Genomics, Inc., today announced ... of its DNA library preparation products, including the ... ThruPLEX Plasma-seq kit. ThruPLEX Plasma-seq has been optimized ... NGS libraries for liquid biopsies--the analysis of cell-free ... applications in cancer and other conditions. Eurofins Scientific ...
(Date:10/27/2015)... NEW YORK , Oct. 27, 2015 ... the major issues of concern for various industry verticals ... This is due to the growing demand for secure ... practices in various ,sectors, such as hacking of bank ... concerns for electronic equipment such as PC,s, laptops, and ...
Breaking Biology News(10 mins):
(Date:11/27/2015)... 27, 2015 /PRNewswire/--  Mallinckrodt plc (NYSE: MNK ... it has closed the sale of its global contrast ... NYSE Euronext) in a transaction valued at approximately $270 ... and a total of approximately 1,000 employees spread across ... St. Louis area. This entire workforce and ...
(Date:11/27/2015)... 27, 2015 ... of companion diagnostics is one of the ... with pharmaceutical companies and diagnostic manufacturers working ... . --> ... on global cancer biomarkers market spread across ...
(Date:11/26/2015)... , England , November 26, 2015 ... Lightpoint Medical, an innovative medical device company specializing in imaging ... grant from the European Commission as part of the Horizon ... the company to carry out a large-scale clinical trial in ... -->      (Logo: , --> ...
(Date:11/25/2015)... 25, 2015  PharmAthene, Inc. (NYSE MKT: PIP) announced ... stockholder rights plan (Rights Plan) in an effort to ... (NOLs) under Section 382 of the Internal Revenue Code ... PharmAthene,s use of its NOLs could be substantially limited ... in Section 382 of the Code. In general, an ...
Breaking Biology Technology: