{"id":2257,"date":"2023-07-18T19:48:51","date_gmt":"2023-07-18T23:48:51","guid":{"rendered":"https:\/\/cqdm.org\/en\/news-and-events\/dimer-interference-a-novel-approach-to-develop-galectin-7-specific-inhibitors-to-treat-triple-negative-breast-cancer\/"},"modified":"2024-09-25T16:25:44","modified_gmt":"2024-09-25T20:25:44","slug":"dimer-interference-a-novel-approach-to-develop-galectin-7-specific-inhibitors-to-treat-triple-negative-breast-cancer","status":"publish","type":"post","link":"https:\/\/cqdm.org\/en\/news-and-events\/dimer-interference-a-novel-approach-to-develop-galectin-7-specific-inhibitors-to-treat-triple-negative-breast-cancer\/","title":{"rendered":"Dimer Interference: A novel Approach to Develop Galectin-7-Specific Inhibitors to treat Triple-Negative Breast Cancer"},"content":{"rendered":"\n

Challenge:<\/strong> Galectins are a family of lectin proteins implicated in tumor progression and immune evasion. When produced in excess by cancer cells, galectins can form homodimers and bind glycans on the surface of T cells. This suppresses the local and systemic immune response in patients, helping tumors to escape immune surveillance and limiting the efficacy of immuno-oncology treatments. To date, most efforts to identify anti-galectin therapeutics have focused on drugs that inhibit binding of galectins to cell surface receptors via their carbohydrate recognition domain (CRD). Unfortunately, most of these attempts have failed.<\/p>\n\n\n\n

Solution:<\/strong> This project aims to develop a novel class of anti-cancer drugs that specifically inhibit the dimerization of galectins as a means to disrupt their protumorigenic activity. This new mechanism of action is an alternative and\/or complementary solution to CRD inhibitors for cancer treatment. As proof of concept, the project has focused on Galectin-7 (Gal-7), a validated target expressed at high levels in aggressive forms of triple-negative breast cancer. Using a rational design approach, the team has developed two classes of inhibitors: \u201cdimer interfering peptides\u201d (DIPs) and camelid nanobodies (Nbs) to selectively target Gal-7 dimerization and consequently, its functional activity in vitro.<\/p>\n\n\n\n

Achievements\/Impact:<\/strong> The team has identified four distinct DIP hits and improved their pharmacokinetic properties and potency. In parallel, a platform was used to develop Gal-7-specific single domain nanobodies that have been humanized. Twelve Nbs were identified as hits following an initial screening of a non-immune recombinant camelid antibody synthetic library. Like DIPs, these Nbs are highly specific and have the potential to inhibit Gal-7 via at least two mechanisms of actions, including dimer-interference.<\/p>\n\n\n\n

Once validated in animal tumor models, the approach could serve as a template to generate inhibitors against a broad range of galectins implicated in the initiation and progression of cancer, including triple-negative breast cancer.<\/p>\n\n\n\n

Principal Investigator:<\/strong>
Yves St-Pierre
<\/strong>INRS-Institut A. Frappier<\/td><\/tr>
Co-investigators<\/strong>
David Chatenet<\/strong>
INRS-Institut A. Frappier
Nicolas Doucet<\/strong>
INRS-Institut A. Frappier<\/td><\/tr>
Completed <\/strong><\/strong><\/strong><\/strong><\/strong>Project<\/strong><\/td><\/tr>
$ 264,000 \/ 2 years<\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/td><\/tr>
Supported by CQDM through:<\/strong>
<\/strong>– Pfizer
– GSK
– Janssen
– Norvartis
– MESI
– RCE-E<\/td><\/tr><\/tbody><\/table><\/figure>\n","protected":false},"excerpt":{"rendered":"

Challenge: Galectins are a family of lectin proteins implicated in tumor progression and immune evasion. When produced in excess by cancer cells, galectins can form homodimers and bind glycans on the surface of T cells. This suppresses the local and systemic immune response in patients, helping tumors to escape immune surveillance and limiting the efficacy…<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-2257","post","type-post","status-publish","format-standard","hentry","category-our-news"],"acf":[],"_links":{"self":[{"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/posts\/2257","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/comments?post=2257"}],"version-history":[{"count":1,"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/posts\/2257\/revisions"}],"predecessor-version":[{"id":4793,"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/posts\/2257\/revisions\/4793"}],"wp:attachment":[{"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/media?parent=2257"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/categories?post=2257"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/tags?post=2257"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}