Grant: Project Grant

In Canada, breast cancer (BC) is the most common cancer in women accounting for 26% of all newly diagnosed cancers. While many therapeutic options for early stage BC can be curative (including radiation therapy, breast-sparing surgery or mastectomy), the treatment of recurrent BC (present in 10-20 % of BC patients) can be clinically challenging (and includes chemotherapy, surgery and/or radiation therapy). Novel combinations of existing therapies offer an exciting opportunity to enhance the killing of BC cells while at the same time avoiding the development of resistance to therapies, which can occur rapidly when treating patients with a single agent. In the proposed research project, two anti-cancer drugs will be encapsulated into a type of nanoparticle called a liposome. Liposomes containing various drugs are currently used in the treatment of breast, ovarian and other cancers. Our liposome nanoparticles have been specially designed so that the drugs will only be released when the temperature exceeds that of normal body temperature. We will increase drug exposure to tumor by increasing the tumor temperature using an ultrasound machine. This technique will allow for a significant amount of the two drugs to be released at the tumor site and minimize any potential side effects in normal tissues. The two drugs we are delivering, doxorubicin and alvespimycin, act on cancer cells by different mechanisms. Preliminary studies by our group have shown that the combination of these two drugs is synergistic and highly efficacious in killing a range of BC cells. Given their synergistic effect, combining the two drugs allows us to reduce the total dose of doxorubicin by at least 20 fold. This is important because doxorubicin is known to have significant side effects including cardiotoxicity. This nanoparticle therapy will also be combined with targeted radiotherapy to offer an exciting combination-based approach for the treatment of recurrent breast cancer in the chest wall.