Cachexia is an underexplored and yet devastating consequence of cancer that is the cause of 20% of all cancer related deaths. Cachexia inducing tumors cause a `wasting away' of the body. Defined as a weight loss of 5% over 3 to 6 months, the condition is associated with poor treatment outcome, fatigue, and extremely poor quality of life. Because of the multi-factorial characteristics of this condition, it has been difficult to understand the impact of the tumor on body organs, and the sequence of events that leads to this lethal condition. To date there are no known cures for this condition. Current molecular and functional imaging approaches are ideally suited to understand critical metabolic changes in the body with the onset of cachexia. Since the syndrome occurs with the highest frequency and severity in pancreatic cancer, we intend to use molecular and functional imaging to understand cancer-induced cachexia and the cachexia cascade in human pancreatic cancer xenografts and human subjects.
In Aim1 we will use a myoblast-based reporter system to detect the onset of cachexia in human xenograft models of pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer, and follow temporal changes in organ metabolites noninvasively with 1H MRSI, and in extracts of organs, muscle, and serum with high resolution 1H MRS.
In Aim 2 we will validate the most easily translatable 1H MRS indices identified in Aim 1 in a pilot study of 20 normal volunteers, 38 non- cachectic PDAC patients, and 38 cachectic PDAC patients, and evaluate changes in serum in retrospective samples from a data bank, and in prospective studies from the PDAC patients. The studies will reveal new perspectives of this condition that may, in the future, lead to effective treatments. The ability to noninvasively detec this condition early on with noninvasive imaging, preferably before or with minimal weight loss, will provide the opportunity to treat the condition before it becomes refractory, design and optimize therapeutic strategies, and detect response to such treatments.
Cachexia induced by cancer is one of the most under explored and yet devastating consequences of cancer, and is the cause for 20% of all cancer related deaths. Cachexia-induced weight loss of 5% over 3 to 6 months is associated with poor treatment outcome, fatigue and poor quality of life, and a weight loss of 30% is frequently lethal. The ability to reverse or control this condition would have a significant impact on treatment outcome, quality of life, and mortality, but to date there are no known cures for this condition. I this application, we will use metabolic imaging in combination with molecular characterization to understand cancer-induced cachexia and the cachexia cascade in pancreatic cancer xenograft models and human subjects.
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