Grant: Operating Grant

THE OBJECTIVE is to protect the heart from injury including from cancer therapy. Heart disease is the single leading cause of death and disability in Canada and its incidence is increasing worldwide. Many factors contribute to an overall risk for heart disease. Some are modifiable, like behaviors, and some are not, like gender or age. Another risk comes from damage done as a side effect of being treated for another disease like cancer. Doxorubicin is a drug used with others to treat a variety of cancers. THE PROBLEM is that doxorubicin like many anti-cancer drugs attacks the heart and this can happen during and even after only one course of treatment. As a result, as many as one in five women treated for breast cancer may suffer heart damage, even heart failure. Even in survivors, often children, there is a real risk that heart problems can develop several years after the cancer therapy is over. WE BELIEVE these drugs do damage, in part, because they attack the heart's own defense mechanism, including growth or survival factors like FGF-16, which is relatively heart-specific after birth and appears to have protective properties. Thus, it might make an excellent supplement that would provide some protection from doxorubicin, or efforts need to be made to maintain or increase our own levels of FGF-16. In the last year, WE SHOWED that FGF-16 will protect the pumping ability of the heart from damage caused by doxorubicin. NOW WE WANT TO confirm FGF-16 has a protective effect on heart muscle cells but not cancer cells. We also want to overproduce FGF-16 in the heart of a mouse to see if it is stored in the heart and not released into the blood supply, and is available to provide additional protection to the heart against anti-cancer drugs. We also want to see if we can find out how FGF-16 is normally made in the heart and whether we can identify a way to maximize levels in the presence of anti-cancer drugs as another way of offering protection from heart injury.