Exercise medicine for cancer cachexia: targeted exercise to counteract mechanisms and treatment side effects

Abstract

Purpose Cancer-induced muscle wasting (i.e., cancer cachexia, CC) is a common and devastating syndrome that results in the death of more than 1 in 5 patients. Although primarily a result of elevated inflammation, there are multiple mechanisms that complement and amplify one another. Research on the use of exercise to manage CC is still limited, while exercise for CC management has been recently discouraged. Moreover, there is a lack of understanding that exercise is not a single medicine, but mode, type, dosage, and timing (exercise prescription) have distinct health outcomes. The purpose of this review was to examine the effects of these modes and subtypes to identify the most optimal form and dosage of exercise therapy specific to each underlying mechanism of CC. Methods The relevant literatures from MEDLINE and Scopus databases were examined. Results Exercise can counteract the most prominent mechanisms and signs of CC including muscle wasting, increased protein turnover, systemic inflammation, reduced appetite and anorexia, increased energy expenditure and fat wasting, insulin resistance, metabolic dysregulation, gut dysbiosis, hypogonadism, impaired oxidative capacity, mitochondrial dysfunction, and cancer treatments side-effects. There are different modes of exercise, and each mode has different sub-types that induce vastly diverse changes when performed over multiple sessions. Choosing suboptimal exercise modes, types, or dosages can be counterproductive and could further contribute to the mechanisms of CC without impacting muscle growth. Conclusion Available evidence shows that patients with CC can safely undertake higher-intensity resistance exercise programs, and benefit from increases in body mass and muscle mass.

Perspectives of Health Care Professionals on Multimodal Interventions for Cancer Cachexia

“… 7–10 However, cancer cachexia is potentially preventable and cachexia-related problems and symptoms can be managed by patient-tailored nutritional support when addressed in a timely manner, 13 , 14 and patients with cancer cachexia may benefit from exercise programs to increase skeletal muscle mass and improve physical function. 15 , 16 …”

Protein Turnover in Skeletal Muscle: Looking at Molecular Regulation towards an Active Lifestyle

“…Still, in a rat model of cancer that develops cachexia, treadmill exercise was shown to prevent and counteract muscle loss, an effect that was associated with exercise-induced lower tumor malignancy and the decrease of circulating pro-inflammatory cytokines [53]. Eccentric resistance exercise has a higher anabolic effect in type II fibers (the type of muscle fibers more susceptible to atrophy in cachexia) compared to concentric and to eccentric combined to concentric exercise (reviewed by [23]). Moreover, the type of protein that is synthetized depends on the type of exercise.…”

“…Indeed, exercise training has been recommended to preserve or increase the SkM mass in subjects at risk of muscle wasting. Resistance training is a well-established exercise mode that stimulates myofibrillar protein synthesis; however, endurance training has been more prescribed for preventing muscle wasting [23]. According to Jee et al [52], only high intensity endurance training preserved mice SkM mass (compared to moderate intensity).…”

“…Exercise (particularly resistance training) is an intervention that modulates protein turnover towards increased SkM mass [4,19]. Their therapeutic value has been investigated in the set of aging and wasting conditions such as cachexia associated with chronic diseases [23]. Herein, we review and update the molecular players and signaling pathways implicated in the regulation of protein turnover during periods of increased or decreased mechanical loading.…”

Impact of cancer cachexia on respiratory muscle function and the therapeutic potential of exercise

“…Indeed, endurance training is known to improve the oxidative capacity of muscle in healthy individuals by enhancing mitochondrial biogenesis and increasing glycogen content (Burgomaster et al., 2007 , 2008 ). Considered in the context of cachexia, Mavropalias and colleagues ( 2022 ) suggested that the benefits of endurance exercise may be intensity dependent, with shorter duration, higher intensity training providing the most promise. Conversely, low‐intensity continuous training is hypothesised to be a less than optimal approach due to its higher energy demands (Bloomer, 2005 ), potentially exacerbating the cachectic condition.…”