For several decades, researchers have known that a class of proteins called galectins has been linked to the spread of cancer, but attempts to create a treatment targeting these proteins have met with little success. Now, a GlycoNet research team is narrowing in on a new drug that targets a protein in this family.
The investigators – Yves St-Pierre, Nicolas Doucet and David Chatenet, all based at the Institut National de la Recherche Scientifique – have discovered a potential drug that will inhibit one of these dangerous proteins, called galectin-7, which is often present in breast cancer and ovarian cancer.
“We found that this protein was actually making a difference between non-metastatic cancer cells and highly-metastatic cancer cells,” St-Pierre explains, meaning that when cancer cells expressed galectin-7, the cancer was more aggressive and more likely to spread. “These proteins recognize the cancer-killing immune cells and kill them, so it is a major obstacle to treatment and that is why we’re targeting it.”
After studying galectins for more than a decade, St-Pierre learned that galectin proteins tend to link together, forming what is called a dimer, which is important to the protein’s biological function.
“We thought, ‘how can we disrupt this dimer?’ We thought if we could prevent these proteins from sticking together, it should inhibit its biological activity,” St-Pierre says. He and his colleagues designed and synthesized peptides, or small molecules for therapeutic purposes, with the goal of disrupting the dimerization of galectin-7.
“It turned out these peptides were very effective. Not only could the peptide disrupt the dimer, but it was capable of destroying galectin-7’s biological activity. It could prevent the ability of galectin-7 to kill the immune cells.”
While past researchers had tried to inhibit galectins before, St-Pierre notes that this project is unique because it has a new target – the protein’s dimerization – and it is specific to galectin-7.
“There are about 15 of these galectins and some of them increase cancer progression, but some of them are actually good for the patient. So it’s very important to target the galectins specifically. One of the problems in the past is that people were designing inhibitors that were not specific enough.”
This can also allow for precision medicine, as galectin-7 is only expressed in about one of two cancers.
“What we want to do today is look at the patient, look at if the target is there, and treat with the drug that treats the target that is present,” he says.