Pancreatic cancer cachexia: a review of mechanisms and therapeutics

Abstract

Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions.

Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action

“…One of those systems is the NFB-dependent ubiquitin-proteasome pathway which is responsible for degradation of myofibrillar proteins and thus skeletal muscle wasting [18][19][20]. Studies have shown that EPA suppresses the production of pro-inflammatory cytokines such as IL-1, TNF␣ and IL-6 in cancer induced cachexia [21][22][23]. EPA also inhibits the NFB activation by suppressing IÄB kinase activity (IKK, an enzyme that phosphorylate IB and promotes its degradation).…”

Dietary lipids and adipocytes: potential therapeutic targets in cancers

“…It is known that cancer cachexia causes reduction of adipose tissue mass mainly by increasing lipolysis, and hence increases the plasma nonesterified fatty acids and triglyceride contents in a triglyceride/ fatty acid-substrate cycle [59,60]. Tumor necrosis factor-α has been associated with increased lipolysis in adipocytes in cancer cachexia.…”

Animal models of cardiac cachexia

“…They might also trigger an imbalance between the leptin and the ghrelin systems, thus generating food intake alterations [6]. In fact, lack of appetite and malabsorption occur in CC, while leptin and ghrelin are among the most influent hormones regulating energy balance [3].…”