Cachexia is a complex multiorgan syndrome associated with various chronic diseases, characterized by anorexia and increased tissue wasting in the context of chronic inflammation. A specific form of this syndrome, known as cancer cachexia (CC), occurs alongside different types of tumors. The pathogenesis of CC is multifactorial. Inflammatory mediators and hormones released by both tumor and host cells have a relevant role in driving the peripheral catabolic process through several direct mechanisms. Accumulating evidence indicates that the central nervous system (CNS) plays an integral role in the pathogenesis of CC. The hypothalamus has emerged as a critical brain region that senses and amplifies peripheral stimuli, generating inappropriate neuronal signaling and leading to the dysregulation of energy homeostasis under cachexia conditions. Circulating cytokines may act in concert with hormones and neurotransmitters and perturb critical hypothalamic neurocircuits shifting their activity towards the anorexigenic pathway and increase of energy expenditure. This review discusses the mechanisms mediating the hypothalamic homeostatic imbalance in the context of anorexia and cachexia associated with cancer.

In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research.

Cachexia is a complex multiorgan syndrome associated with various chronic diseases, characterized by anorexia and increased tissue wasting in the context of chronic inflammation. A specific form of this syndrome, known as cancer cachexia (CC), occurs alongside different types of tumors. The pathogenesis of CC is multifactorial, with inflammatory mediators and hormones released by either the tumor or the host identified as key drivers of the peripheral catabolic process through several direct mechanisms. Accumulating evidence indicates that the central nervous system (CNS) is also recognized as an integral component in the pathogenesis of CC. Hypothalamus has emerged as a critical brain area that senses and amplifies peripheral stimuli, generating an inappropriate neuronal signaling, leading to deregulation of feeding behavior and impaired control of energy homeostasis. Circulating cytokines may act in concert with hormones and neurotransmitters and perturbate the hypothalamic melanocortin system, shifting its activity towards the anorexigenic pathway and increase energy expenditure. The purpose of this review is to provide insights on the potential mechanisms mediating the hypothalamic inflammation in the context of anorexia and cachexia associated with cancer.