Grant: Project Grant

Although therapies for breast cancer have been improving, it remains a very common problem that patients develop a resistance to their therapy. When this happens there are unfortunately very few alternatives available to clinicians to help those patients and this usually means that the chances of surviving the cancer are greatly reduced. We are working on a new strategy that could help to make a drug that is currently used in the clinic (so we know it is safe) work for breast cancer. Specifically, we are focusing on a cancer drug named Velcade, which works really well for cancers of blood origin, but has proven significantly less efficient at killing other cancers, including breast cancer tumours. Our lab is working towards gaining a better understanding of the role(s) of a protein modification, called 'arginine methylation'. This modification of proteins is a 'flag' that is added to certain proteins in our cells. This mark in turn can change how the protein will work, and can even confer new functions to it. This work has led to the discovery that arginine methylation is somehow involved in the way that Velcade works to kill cancer cells, and in turn, that tinkering with this modification in breast cancer cells using various strategies can in fact make them more sensitive to this drug. We thus propose in the current project to assess the feasibility of a novel strategy to sensitize breast cancer cells to the chemotherapeutic drug Velcade. The proposed research will first aim to assess the relative whether our strategy works in all types of breast cancer or just in a specific subtype. We will also pursue experiments to gain a better understanding of how blocking arginine methylation can make Velcade work better in breast cancer cells. Finally, we will use mouse models of breast cancer to determine whether our strategy can also work in the context of a whole animal. This project could enable the development of alternative therapies for patients developing resistance.