The Biological Mechanisms of Cancer-Related Skeletal Muscle Wasting: The Role of Progressive Resistance Exercise

Cancer results in perturbations in skeletal muscle protein metabolism leading to muscle wasting. Although severe wasting is seen primarily in persons with advanced malignancies, a number of cancer patients show some degree of wasting at presentation. Although cancer-related skeletal muscle wasting is attributable, in part, to decreased muscle protein synthesis, its primary cause appears to be increased muscle protein degradation. Although several proteolytic systems may be involved, compelling evidence suggests that the major system responsible for skeletal muscle protein degradation in cancer is the ATP-dependent ubiquitin— proteasome system. Other contributing factors include proinflammatory cytokines and the tumor-released proteolysis-inducing factor. Decreased physical activity and decreased nutritional intake may also play a role. Cancer-related skeletal muscle wasting is clinically significant because of its profound effects on functional outcomes and quality of life. Nevertheless, no specific interventions have proved to be effective in preventing or reversing the problem. Interventions such as nutritional supplementation and appetite stimulants are only partially helpful. A nonpharmacologic intervention that may attenuate cancer-related skeletal muscle wasting is progressive resistance exercise training (PRT). PRT is a potent stimulus of growth in muscle mass and strength. PRT may attenuate cancer-related skeletal muscle wasting by downregulating the activity of proinflammatory cytokines and by increasing the phosphorylation of intramuscular amino acid—signaling molecules. This article discusses several cancer-related skeletal muscle wasting mechanisms and proposes how PRT might attenuate muscle wasting by counteracting some of these mechanisms.