Sugar research might help answer the unanswered in cancer
Ali Chou • Posted: February 4, 2021 • Updated: April 30, 2021
Canadian scientists from GlycoNet are making strides in cancer research through gaining a deeper understanding of sugars in our body.
Scientists at GlycoNet are taking the challenge by making the invisible visible. In other words, they look closely at the structure and the changes of sugars on tumor cells, investigate the interactions between these sugars and other biomolecules in our body, and leverage this knowledge to develop technologies that can recognize or attack cancer cells when our immune system fails to do so.
Every cell in our body is covered in specialized sugars. Unlike table sugar, these sugars are attached to cell surfaces and serve as communication markers that tell our body where the cells belong to or whether certain cells are alien. Cancer cells are masters of deception. By manipulating the sugars on their surface, cancer cells not only can evade from the immune system, but also direct other cells in the body to help them spread. All these misbehaviours facilitated by changes on cell surface sugars are either invisible to our immune defense or deliberate misdirection of our immune cells, and fighting against that level of cellular deception is a difficult task.
However, scientists at GlycoNet are taking the challenge by making the invisible visible. In other words, they look closely at the structure and the changes of sugars on tumor cells, investigate the interactions between these sugars and other biomolecules in our body, and leverage this knowledge to develop technologies that can recognize or attack cancer cells when our immune system fails to do so.
Below are several multidisciplinary cancer projects from GlycoNet. Each of these projects consists of a team of Canadian scientists who are making strides in cancer research through gaining a deeper understanding of sugars in our body.
A short animated video explaining the secret life of carbohydrates and why glycomoics is important to understand health and diseases.
GlycoNet researcher Karla Williams from the University of British Columbia explains how sugars in the blood hold clues to detecting aggressive cancer.
The sugar-binding protein that suppresses the immune system
Dr. Yves St-Pierre recently presented at Research Canada’s “Cancer Gone: The Research and Innovation that Thinks It Can” on April 29, 2021
Sugar-binding proteins being studied: galectins
Disease focus: breast cancer
Sugar-binding proteins are just as important as sugars when it comes to cancer research. For example, galectins, a class of sugar-binding protein with immunosuppressive properties, are highly expressed in cancer cells. As these proteins suppress the immune system, cancer cells become more invasive and can grow and spread to other sites in the body. GlycoNet researchers Yves St-Pierre, David Chatenet, and Nicolas Doucet from the Institut national de la recherche scientifique, together with industry partners, are developing technologies to specifically inhibit the action of galectins. This project lays the foundation for a new generation of cancer immunotherapy specifically targeting triple negative breast cancer, an aggressive form of breast cancer currently with very limited treatment options.
The sugars that help cancer cells evade immunity
Sugar being studied: sialic acids
Disease focus: pancreatic cancer
One hallmark between normal and cancer cells is that the surface of a cancer cell is covered by many more sialic acids. This abnormally high amount of sugar on the cell surface may be the reason why our immune system cannot identify cancer cells as “non-self.” Researchers including Matthew Macauley, Ratmir Derda, John Klassen, Todd McMullen, and Lisa Willis from the University of Alberta are working to unveil the mechanisms by which sialic acids use to evade immunity. By identifying the type of a family of immune proteins (called Siglecs) that interact closely with sialic acids on cancer cells, the team aims to discover new therapeutic targets to combat cancer and establish new biomarkers for diagnoses.
The sugars that are important for accurate early diagnoses
Sugar being studied: polysialic acids
Disease focus: prostate cancer
Early detection of prostate cancer still needs significant improvement. About 70 per cent of low-risk individuals for prostate cancer could be spared an invasive biopsy. GlycoNet researcher Hon Leong from Sunnybrook Hospital is implementing a blood test in the urology clinic by combining it with MRI imaging of the prostate, which may increase accuracy of early diagnoses to 95% or higher. The technology behind the blood test is based on the detection of polysialic acid — a biomarker for aggressive prostate cancer—from the cell fragments shed by cancer cells in a patient’s blood. The project will help individuals who are on active surveillance to avoid unnecessary biopsies.
The sugars that hold clues to a new companion diagnostic
Sugar being studied: different types sugars on tumor cell fragments
Disease focus: breast cancer
Breast cancer could be detected earlier than current techniques permit using a unique glycomics-based technology to uncover hidden clues in the blood. A team project led by Dr. Karla Williams from the University of British Columbia and Dr. Lara Mahal from the University of Alberta is finding new, sugar-based markers to identify individuals with breast cancer. The team is developing a profile of the sugar composition on cell fragments shed by tumor tissue from breast cancer patients. Then, by comparing this sugar profile to that of healthy individuals, the team aims to develop a “fingerprint” of healthy versus diseases status that can be used as a companion diagnostic for mammography.
Better routes to making sugar derivatives used to treat cancer
Sugar being studied: nucleoside analogues
Disease focus: different types of cancer
Many existing FDA-approved drugs used to treat leukemia, skin cancer, breast, pancreatic, lung and ovarian cancers are based on the sugars called nucleoside analogues. Although these sugars are effective in inhibiting cancer cell growth, their synthesis is not the most efficient. GlycoNet scientist Robert Britton from Simon Fraser University, in collaboration with Merck, has developed a new process that cuts ten-plus step syntheses, which can take several months to complete, to three or four steps, which would take only a week or so. With this process, scientists may be able to create more varieties of potential anticancer drugs much quicker and with great diversity in structure than with traditional synthetic methods, making drug discovery faster.
A sugar derivative that attacks pancreatic cancer cells
Sugar being studied: nucleoside analogues
Disease focus: pancreatic cancer
Pancreatic cancer patients have a five-year survival rate of 5%. A team of medicinal chemists, cancer experts and molecular biologists is developing drug candidates against pancreatic cancer cells unresponsive to existing therapies. These novel molecules are nucleoside analogues designed to interfere with the bioenergetics of mutated cancer cells, stopping their growth and leading to their death. Led by Yvan Guindon from Institut de Recherches Cliniques de Montréal, John Bell and Mona Nemer from University of Ottawa, the project aims to advance the development of drugs targeting the metabolism and machinery of tumor cells growth in pancreatic cancers.
Read more about our cancer projects here.
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