Cancer Cachexia as Multi-organ Syndrome

Samenvatting

Cancer cachexia is characterized by severe weight loss, muscle wasting, and fatigue that often occurs in advanced stages of cancer. This condition affects many organs including muscle, intestine, and the hypothalamus. This thesis aimed to investigate a fundamental aspect of this multi-organ syndrome, with emphasis on the role of the gut-brain axis and the role of mitochondrial dysfunction in skeletal muscle. In vitro studies revealed molecular mechanisms, while animal studies validated multi-organ changes and assessed the genetic editing treatments. Additionally, a human observational study identified the potential predictive value of early-stage mitochondrial dysfunction in the progression of colon cancer. Central to our conclusion is the role of systemic inflammation, fuelled by tumor-derived prostaglandin E2 and gut-derived LPS, in the interactions among the intestine, hypothalamus, and muscle. These researches provide insight into cancer cachexia's multifactorial nature, suggesting future research directions and therapeutic possibilities to enhance treatment outcomes and patient survival.