Cachexia is a condition of severe body weight loss due to striated muscle wasting associated with chronic diseases, including cancer. Cachexia directly accounts for 20% of cancer patient deaths, and therefore its occurrence is a poor prognosis factor. However, the actual mechanisms responsible for cachectic patient mortality have still not been clearly established. Both skeletal and cardiac muscle wasting occur in cancer cachexia. We and others have shown that exercise counteracts skeletal muscle wasting and increases survival in both animal models and cancer patients. We aim to extend our studies to the other striated muscle (i.e., cardiac muscle) in order to establish a correlation between atrophy of the heart and mortality risk; we also aim to demonstrate if endurance exercise rescues heart homeostasis and function in a murine model of cancer cachexia (C26 colon carcinoma-bearing mice). To this purpose, we will perform a metanalysis on clinical studies to demonstrate the association between the occurrence of cachexia, mortality and the underlying presence of cardiovascular disease states. In the murine model, we will compare the heart composition and function in C26-bearing mice which display or not cachexia; besides, we will study exercise effects on the heart, to see whether aerobic training ameliorates heart condition in the presence of a tumor. The expected results will show: whether cachexia is a reliable indicator of poor patient prognosis due to heart wasting, the need for prevention of cardiovascular diseases as a comorbidity in cachexia, and if exercise exerts beneficial effects on the heart increasing survival.
While the occurrence of cardiac wasting in cancer cachexia is now widely accepted, its clinical relevance is not acknowledged in the presence of a severe disease such as cancer. Cancer cachexia is known to contribute to as many as 20% of the cancer patients¿ deaths, but the ultimate causes of death in cachectic patients are not clear. To the best of our knowledge, this is the first study trying to address heart wasting and failure as a direct cause of death associated with cachexia.
This study may conclude that cachexia is a reliable indicator of poor patient prognosis due to heart wasting and urge for the prevention of cardiovascular diseases. Also, this study may contribute to the tuning of the definition of the diagnostic criteria cachexia, which could include not only ¿skeletal muscle¿ but ¿striated muscle¿ wasting in the future.
The consequences for both basic science studies and the clinical practice would be relevant.
Given the interdisciplinary and international collaboration foreseen for this study (2 centers in Rome, the IRCCS Santa Lucia and Sapienza, and one institution in Paris, Sorbonne University) this study could provide preliminary, yet strong data to support an application for European grants in the near future.