U of M based GlycoNet investigators identify novel anti-cancer agents

By Chardelle Prevatt 

Cancer is the leading cause of death in Canada. According to the Canadian Cancer Society, an estimated 202,400 new cancer cases occurred in Canada in 2016, resulting in over 78,800 deaths. GlycoNet scientists, Drs. Frank Schweizer and Gilbert Arthur, together with a team of University of Manitoba (U of M) researchers, have identified a unique way to potentially treat and cure cancer, using carbohydrate-based antitumor agents.

Increasingly, studies support the idea that cancer stem cells (CSCs) are linked to tumor metastasis and resistance to chemotherapies. Therefore, eliminating CSCs is crucial to successful cancer treatment. In a paper published in the Journal of Medicinal Chemistry, Drs. Schweizer and Arthur, and their U of M collaborators, describe the synthesis of L-sugar analogues of an emerging class of glycolipids called glycosylated antitumor ether lipids (GAELs). In addition, the researchers examine the effects of these GAELs on cancer cells and CSCs and provide some insight on their mechanism of action. The findings reveal that these GAELs have a rare ability to kill CSCs when compared to most clinically used anticancer drugs.

In multicellular organisms, a process known as apoptosis or cell suicide destroys cells that pose a threat to the organism or those that are no longer needed. However, CSCs have developed several mechanisms of escaping apoptosis. This is particularly alarming in aggressive cancers that contain higher concentrations of CSCs.

“Currently, there are very few compounds that actually eliminate CSCs,” said Dr. Schweizer. “GAELs have the ability to kill CSCs by avoiding their defences against apoptosis. However, one challenge is that our bodies would metabolize the D-sugar-based GAELs, preventing the required levels to accumulate.”

“L-GAELs are more metabolically stable,” Dr. Arthur explained. “Therefore, we expect that they can stay much longer in the human body to help inhibit tumor progression and recurrence.”

The researchers are optimistic that future studies on mice models will provide novel insights into the effects of L-GAELs on eliminating CSCs. This may potentially lead to clinically useful antitumor treatments for cancer patients.

To read the full research paper, click here.

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