A Pound of Flesh: What Cachexia Is and What It Is Not

Abstract

Body weight loss, mostly due to the wasting of skeletal muscle and adipose tissue, is the hallmark of the so-called cachexia syndrome. Cachexia is associated with several acute and chronic disease states such as cancer, chronic obstructive pulmonary disease (COPD), heart and kidney failure, and acquired and autoimmune diseases and also pharmacological treatments such as chemotherapy. The clinical relevance of cachexia and its impact on patients’ quality of life has been neglected for decades. Only recently did the international community agree upon a definition of the term cachexia, and we are still awaiting the standardization of markers and tests for the diagnosis and staging of cancer-related cachexia. In this review, we discuss cachexia, considering the evolving use of the term for diagnostic purposes and the implications it has for clinical biomarkers, to provide a comprehensive overview of its biology and clinical management. Advances and tools developed so far for the in vitro testing of cachexia and drug screening will be described. We will also evaluate the nomenclature of different forms of muscle wasting and degeneration and discuss features that distinguish cachexia from other forms of muscle wasting in the context of different conditions.

Histone Deacetylases as Modulators of the Crosstalk Between Skeletal Muscle and Other Organs

“…For instance, insulin resistance correlates with an increase in the anaerobic and glycolytic capacities of muscle, similarly to what happens in obesity and diabetes (Simoneau et al, 1995). On the other hand, age-related sarcopenia is characterized by an increase in the relative amount of slow-twitch fibers and by the atrophy of the fast ones (Gannon et al, 2009;Daou et al, 2020;Berardi et al, 2021).…”

Chemotherapy-Induced Myopathy: The Dark Side of the Cachexia Sphere

“…This is problematic with respect to the clinical compatibility of this paradigm, as the large majority of cancer patients typically receive chemotherapy as part of their treatment strategy. This highlights the need for experimental studies to reflect the synergistic insult from cancer and chemotherapy in the induction of cachectic myopathy [ 15 ]. Models that allow the exploration of both factors in combination, and, using the spectra of chemotherapeutic agents, multi-therapy regimens, and cancer sub-types, are required.…”

“…Cachexia is a multifactorial condition characterised by the loss of body mass and composition (highlighted by lean mass loss, with or without loss of fat mass) and progressive functional impairment [ 14 ]. The centrally afflicted organ in cachexia is skeletal muscle, which is driven by a multitude of factors including metabolic dysregulation; anorexia; systemic inflammation; and insulin resistance [ 15 ]. Skeletal muscle mass is an integral prognostic marker in cancer cachexia diagnosis—this is because increased adiposity de- sensitises the utility of body weight and body mass index (a crude indicator of body composition) during cachexia diagnosis [ 16 , 17 ].…”

“…The result is compromised treatment efficacy (i.e., dose-reduction or treatment cessation) that increases the risk of morbidity and mortality [ 18 ]. Cachectic myopathy is the result of two synergistic insults from each of: (1) cancer–host interactions and (2) chemotherapy toxicity [ 15 , 19 ]. These effects can be acute, yet are most often life-long [ 20 ].…”

Cachectic muscle wasting in acute myeloid leukaemia: a sleeping giant with dire clinical consequences

“…Future studies investigating AML‐derived CIFs will also have the potential to aid development of screening strategies for AML‐specific cachexia risk stratification using biomarkers. Current biomarkers are overtly non‐specific to cancer type and do not delineate the general ratio between pro‐inflammatory and anti‐inflammatory cytokines 64 . However, biomarker strategies for cachexia screening may still be useful in haematological malignancies such as AML, given their current lack of utility.…”