Grant: Canada Postdoctoral Research Award (CPRA) program

Breast cancer is the most common cancer affecting Canadian women, and the spread of the disease (metastasis) remains the leading cause of death. Once breast cancer progresses from an early, localized stage to metastatic spread, survival rates drop drastically. For example, the 5-year survival rate decreases from over 99% to less than 25%. This highlights an urgent need for new therapies that can stop breast cancer from spreading. In my research, I have discovered that two proteins, calpain-1 and calpain-2, play a central role in driving breast cancer progression and metastasis. In laboratory models, tumours lacking these proteins develop about 80% fewer metastases. Unfortunately, no drugs currently exist that can safely and effectively block calpain-1 or calpain-2 in patients' tumours. Developing such inhibitors could open a completely new avenue for breast cancer treatment. In this project, I will use innovative approaches to develop first-in-class inhibitors of calpain-1 and calpain-2. My work will focus on two complementary strategies: (1) modifying a natural inhibitor of calpain to make it more effective and drug-like, and (2) harnessing novel protein degradation technologies to selectively remove calpain from cancer cells. Promising compounds will be tested in biochemical experiments, cancer cell models, and mouse models of breast cancer metastasis. By building on our discoveries and working closely with medicinal chemists and structural biologists, I aim to create novel therapies that target the root drivers of metastasis. The long-term goal is to reduce breast cancer deaths by providing patients, especially those with aggressive forms such as triple-negative breast cancer, with urgently needed treatment options.