Tumor cell anabolism and host tissue catabolism-energetic inefficiency during cancer cachexia

Abstract

Cancer-associated cachexia (CC) is a pathological condition characterized by sarcopenia, adipose tissue depletion, and progressive weight loss. CC is driven by multiple factors such as anorexia, excessive catabolism, elevated energy expenditure by growing tumor mass, and inflammatory mediators released by cancer cells and surrounding tissues. In addition, endocrine system, systemic metabolism, and central nervous system (CNS) perturbations in combination with cachexia mediators elicit exponential elevation in catabolism and reduced anabolism in skeletal muscle, adipose tissue, and cardiac muscle. At the molecular level, mechanisms of CC include inflammation, reduced protein synthesis, and lipogenesis, elevated proteolysis and lipolysis along with aggravated toxicity and complications of chemotherapy. Furthermore, CC is remarkably associated with intolerance to anti-neoplastic therapy, poor prognosis, and increased mortality with no established standard therapy. In this context, we discuss the spatio-temporal changes occurring in the various stages of CC and highlight the imbalance of host metabolism. We provide how multiple factors such as proteasomal pathways, inflammatory mediators, lipid and protein catabolism, glucocorticoids, and in-depth mechanisms of interplay between inflammatory molecules and CNS can trigger and amplify the cachectic processes. Finally, we highlight current diagnostic approaches and promising therapeutic interventions for CC.

Self-assembled nanomicelles for oral delivery of luteolin utilizing the intestinal lymphatic pathway to target pancreatic cancer

“…The body weight of the control group was significantly reduced compared to the treatment group (*** p < 0.001) due to disease-associated cachexia. 36 Furthermore, there was no significant alteration in the mouse weight observed in the LUT, LUT-NP1, and LUT-NP2-treated groups during the treatment schedule, which reflected the antitumor effect of the treatment. Along with the body weight, the tumor volume of all the groups was measured during a complete course of treatment.…”

Molecular Mechanisms of Cachexia: A Review

“…Cancer cachexia is a pathological condition characterized by an imbalance in the equilibrium between anabolic and catabolic processes. Skeletal muscle, which serves as a substantial reservoir of proteins, is regulated by catabolic processes that facilitate the breakdown of proteins or hinder their synthesis, as well as anabolic mechanisms that enhance protein synthesis [15]. Several factors can disturb the equilibrium of skeletal muscle homeostasis.…”

SEOM clinical guidelines for cancer anorexia-cachexia syndrome (2023)

“…Muscle wasting in cachexia arises from a combination of reduced protein synthesis and increased protein catabolism. Lipolysis is triggered by enhanced activation of the central nervous system and by cytokines such as IL-1, IL-6, TNF-α, and TNF-γ, as well as zinc glycoprotein-α [35].…”