Cancer-associated cachexia — understanding the tumour macroenvironment and microenvironment to improve management

Cachexia is a devastating, multifactorial and often irreversible systemic syndrome characterized by substantial weight loss (mainly of skeletal muscle and adipose tissue) that occurs in around 50–80% of patients with cancer. Although this condition mainly affects skeletal muscle (which accounts for approximately 40% of total body weight), cachexia is a multi-organ syndrome that also involves white and brown adipose tissue, and organs including the bones, brain, liver, gut and heart. Notably, cachexia accounts for up to 20% of cancer-related deaths. Cancer-associated cachexia is invariably associated with systemic inflammation, anorexia and increased energy expenditure. Understanding these mechanisms is essential, and the progress achieved in this area over the past decade could help to develop new therapeutic approaches. In this Review, we examine the currently available evidence on the roles of both the tumour macroenvironment and microenvironment in cancer-associated cachexia, and provide an overview of the novel therapeutic strategies developed to manage this syndrome.