Targeting cancer cachexia: Molecular mechanisms and clinical study

Abstract

Cancer cachexia is a complex systemic catabolism syndrome characterized by muscle wasting. It affects multiple distant organs and their crosstalk with cancer constitute cancer cachexia environment. During the occurrence and progression of cancer cachexia, interactions of aberrant organs with cancer cells or other organs in a cancer cachexia environment initiate a cascade of stress reactions and destroy multiple organs including the liver, heart, pancreas, intestine, brain, bone, and spleen in metabolism, neural, and immune homeostasis. The role of involved organs turned from inhibiting tumor growth into promoting cancer cachexia in cancer progression. In this review, we depicted the complicated relationship of cancer cachexia with the metabolism, neural, and immune homeostasis imbalance in multiple organs in a cancer cachexia environment and summarized the treatment progress in recent years. And we discussed the molecular mechanism and clinical study of cancer cachexia from the perspective of multiple organs metabolic, neurological, and immunological abnormalities. Updated understanding of cancer cachexia might facilitate the exploration of biomarkers and novel therapeutic targets of cancer cachexia.

Development of a nutritional screening and assessment indicator system for patients with esophageal cancer in China: Findings from the Delphi method

“…22 The intricate interplay between neoplasms, the tumor microenvironment, and diverse organ systems catalyzes the manifestation of tumor-associated malnutrition within cancer patients. 23 The tumor microenvironment (TME)-composed of cancer cells, assorted stromal cell populations (such as infiltrating immune cells, neutrophils, fibroblasts, and adipocytes), extracellular matrix constituents, soluble factors, and signaling moleculesexerts an instrumental role in inciting systemic inflammation and augmented oxidative stress in cancer patients. 24 Systemic inflammation serves as a fundamental facet in the pathophysiology of tumor-associated malnutrition (cancer cachexia), and its significance is accentuated by global leadership initiative on malnutrition (GLIM) on malnutrition diagnostic criteria.…”

“…The intricate interplay between neoplasms, the tumor microenvironment, and diverse organ systems catalyzes the manifestation of tumor‐associated malnutrition within cancer patients 23 . The tumor microenvironment (TME)—composed of cancer cells, assorted stromal cell populations (such as infiltrating immune cells, neutrophils, fibroblasts, and adipocytes), extracellular matrix constituents, soluble factors, and signaling molecules—exerts an instrumental role in inciting systemic inflammation and augmented oxidative stress in cancer patients 24 .…”

“…Additional molecules, such as TNF-α, ghrelin, and PTHrP, facilitate the regulation of appetite and dietary intake via diverse mechanisms. 21,23,28 During the nascent stages of cancer-related malnutrition, referred to as cancer cachexia, an escalation in visceral organ and tumor mass represents one variant of the body's increased resting energy expenditure. The liver's seminal role in energy metabolism encompasses the handling of the body's three principal fuel substrates: glucose, fats, and proteins.…”

“…The resultant release of amino acids into the bloodstream further augments tumor cells' utilization of aerobic glycolysis metabolic pathways, thereby enhancing tumor growth and hastening energy depletion. 23 Within the patient population afflicted by cancer-related malnutrition (cancer cachexia), the onset of lipolysis is observed to precede muscular atrophy. A cohort study conducted in Sweden, evaluating the alterations in body composition among patients diagnosed with gastrointestinal solid neoplasms, discerned that the depletion of adipose tissue occurred at an accelerated rate compared to the loss of lean body mass in individuals experiencing progressive cachexia.…”

“…It not only exerts a direct influence on the brainstem's feeding center, eliciting anorexia, but also modifies the body's metabolic pathways, resulting in muscle and fat depletion. Additional molecules, such as TNF‐α, ghrelin, and PTHrP, facilitate the regulation of appetite and dietary intake via diverse mechanisms 21,23,28 …”