Cells Publication

| 10 October 2025

Congratulations to Danielle Harper and Ivan Shapovalov for their recent publication in Cells, which validates the Calpain-1 and Calpain-2 proteases as potential therapeutic targets whose inhibition could provide protection against metastasis in aggressive tumors like triple negative breast cancer.

With contributions from previous trainees, James MacLeod, Jenny Min and Samantha Cockburn, Dani and Ivan used gene editing to knock out and then rescue expression of these classical calpain isoforms in human breast cancer cells and then evaluate the effect of this genetic manipulation on their ability to form metastatic tumors in xenograft mouse models. They show that genetic loss of Calpain-1 and Calpain-2, or their pharmacologic inhibition, compromises the ability of these cancer cells to migrate in vitro and to metastases in vivo from tumors to the lungs after orthotopic engraftment into the mammary glands of mice.

These studies provide the target validation justification that Ivan is using to move ahead with the development of calpain inhibitors suitable for translation to the clinic. Suppression of the metastatic ability of cancer cells could have an enormous impact on the survival of cancer patients with late-stage disease.

This work was supported by a grant from the CIHR. Read the published work here: Calpain-1 and Calpain-2 Promote Breast Cancer Metastasis - PMC

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