Pancreatic cancer is currently the fourth most common cancer causing death in the United States, with mortality rates nearly equaling incidence rates. Adenocarcinoma histologically constitutes approximately 90% of pancreatic tumors with current 5-year survival rates of only 4%. Successful surgical resection can improve survival rates to 25%, but tumor recurrence is common. A compounding feature of pancreatic cancer is the high incidence of the cachexia syndrome, a complex metabolic disorder characterized by extreme weight loss due to the gross depletion of adipose and skeletal muscle tissues. Unlike starvation which reduces fat content but where skeletal muscle is preserved, in cachexia neither fat nor muscle is spared. This may partly explain why nutritional supplementation alone stimulates transient weight gain due to accumulation of fat, but is not sufficient to influence lean mass, quality of life and/or survival. Pancreatic cancer patients typically lose greater than 10% of their pre-illness body weight, which can decline to 25% near time of death. Although weight loss represents the current benchmark standard to diagnose cachexia, too often this occurs in advanced stages of pancreatic cancer where anti-cachexia intervention may already be limiting. Intervention prior to the onset of weight loss may have therapeutic benefits, but this strategy is currently hindered by the inability to sufficiently recognize prognosticators of the cachexia syndrome. Clinical and molecular markers have been identified, but their validation has mainly been restricted to tissue culture systems and animal models of cancer cachexia. Therefore, there is a clear need in pancreatic cancer research to validate these current markers as well as to identify novel markers that may lead to effective early anti-cachexia treatment. To make this determination, the following two specific aims will be performed: 1) to validate the current markers of cachexia in human pancreatic cancer; and 2) to screen for novel early markers of cachexia in pancreatic cancer. Completion of these aims should advance our understanding of pancreatic cancer cachexia and potentially also affect treatment options to improve quality of life and/or survival. ? ? ?
| He, Wei A; Berardi, Emanuele; Cardillo, Veronica M et al. (2013) NF-?B-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia. J Clin Invest 123:4821-35 |
