Grant: Operating Grant

This project aims to develop a new radiation treatment for breast cancer that is resistant to trastuzumab (Herceptin). The introduction of Herceptin for treatment of HER2-positive breast cancer has been a major advance. However, only 1 in 2 patients respond to this treatment and almost all patients who initially respond to Herceptin develop resistance within a year. In the proposed project, a team of scientists will combine their unique expertise to design new treatments for overcoming Herceptin-resistance. These treatments will be composed of antibodies that recognize proteins on breast cancer cells linked to polymers that incorporate multiple binding sites for radioisotopes that increase their potency for killing tumour cells. The polymers will also include a function that delivers the radiation directly to the nucleus or DNA of tumour cells to further increase their effectiveness. The radioisotopes to be used emit short range radiation that kills only single tumour cells thus minimizing normal tissue toxicity or longer range radiation that can kill many cells within a tumour. These new treatments will first be tested for killing breast cancer cells in culture, then their ability to localize in breast cancer tumours in mice will be examined. Finally, the treatments will be tested for their effectiveness and toxicity in mice with human breast cancer tumours that are resistant to Herceptin. Through a collaboration with a clinical trials group in Ontario, the team plans to advance these new treatments to patients with breast cancer in the future if the results of the research are promising.