A Nonhuman Primate Model for Doxorubicin-induced Cardiotoxicity
A nonhuman primate model for testing whether your novel therapeutic can mitigate doxorubicin-induced cardiotoxicity.
Doxorubicin, an anthracycline chemotherapeutic, is a key drug for treating patients with certain cancers, including lymphoma, leukemia and breast cancer. The use of doxorubicin, however, is often limited due to it causing serious side effects, including cardiotoxicity and heart failure1. Doxorubicin-induced cardiovascular disease is the leading cause of morbidity and mortality for cancer patients surviving five or more years. Patients who develop congestive heart failure have a one-year survival rate of less than 50%2-4.
Current prevention or treatment options for anthracycline-induced cardiotoxicity are limited to adjusting the patient’s exposure to the therapeutic, which reduces its potential use.
The underlying mechanisms of doxorubicin-induced heart failure are not well understood. For example, the leading hypothesis of toxic-free radicals driving doxorubicin-induced heart disease does not fully describe the complete spectrum of the effect5.
Research has shown that non-muscular myocardial components such as the extracellular matrix are essential to maintaining cardiac structure and function6. However, the effects of doxorubicin on these components have not been extensively studied.
Researchers at Wake Forest Baptist have developed a model of doxorubicin-induced heart failure in nonhuman primates, specifically African green monkeys. They have accurately and noninvasively evaluated the progression of myocardial injury using cardiovascular magnetic resonance. Specialized mapping techniques have been used to characterize extracellular matrix damage—specifically fibrosis (see Figure 1)—and link it to decreased cardiac function as measured by more traditional modalities like echocardiography.
With this unique animal model and imaging techniques, the mechanisms and effects of therapeutics or other interventions on chemotherapeutic-induced heart failure can be evaluated in vivo.
- Test drug efficacy in established translational model
- Corroborate imaging data with histopathological and biochemical end-points not feasible in human studies
- Mechanisms and effects of interventions on doxorubicin-induced heart failure can be tracked over time with disease progression