Pre-clinical design of a novel targeted and personalized treatment against Sortilin-positive triple negative breast cancers

Challenge: Triple negative breast cancer (TNBC) accounts for 15 to 20% of diagnosed breast tumors. This type of breast cancer is particularly aggressive and associated with a high risk of recurrence, especially in the first five years after diagnosis. TNBC treatment is limited to chemotherapy that can be combined with surgery and/or radiotherapy. Targeted therapy in not currently a therapeutic option because of the lack of specific drug target biomarkers.

Solution: Dr. Annabi’s team is focusing on the development of a new targeted therapy for the treatment of TNBC overexpressing the Sortilin protein receptor. This receptor, highly expressed at the surface of breast cancer cells and in larger amounts than in healthy cells, is an important player in the processes of cancer cell proliferation and in the formation of metastases. It is also a gateway for internalisation of molecules circulating in the body. In collaboration with Theratechnologies, Dr. Annabi’s team is developing a peptide (KA-peptide) that can target the Sortilin receptor while carrying an anti-cancer drug (docetaxel). This conjugated molecule called DoceKA can be internalized in breast cancer cells, using Sortilin as a gateway, thus allowing the neutralization of breast cancer cells. Preliminary results indicate that this new conjugated anticancer molecule demonstrates improved efficacy and specificity, while having few side effects compared to current therapeutic treatments.

Expected achievements/Impact : In this project, the research team will further validate Sortilin as a chemotherapeutic target, characterize the lead candidate DoceKA in TNBC in vitro and in vivo models, and analyze its pharmacokinetics and stability in biological fluids. The resulting data will create significant value for Theratechnologies, as it will position one of their lead products against breast cancer to a stage of readiness to embark in the critical IND-enabling pre-clinical studies, and then clinical Phase Ia/Ib studies. The project is fully aligned with Theratechnologies objectives focused on the translation of early-stage discoveries from the vast reservoir of Canadian academic and Biotech innovations into economic prosperity and improved health outcomes.