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In this review, we focus on the different mediators of impaired anabolism and upregulated catabolism that alter the skeletal muscle homeostasis resulting in the wasting of cancer cachexia. We present recent evidence of targeted treatment modalities from clinical trials along with their potential mechanisms of action. We also report on the most current evidence from randomized clinical trials using multimodal treatments in patients with cancer cachexia, but also the evidence from head and neck cancer\u2010specific trials. A more complete understanding of the pathophysiology of the syndrome may lead to more effective targeted therapies and improved outcomes for patients. \u00a9 2015 Wiley Periodicals, Inc. 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