The pathophysiology of cancer-mediated cardiac cachexia and novel treatment strategies: A narrative review

Abstract

Significance: Two of the leading causes of death worldwide are cancer and cardiovascular diseases. Most cancer patients suffer from a metabolic wasting syndrome known as cancer-induced cardiac cachexia, resulting in death in up to 30% of cancer patients. Main symptoms of this disease are severe cardiac muscle wasting, cardiac remodeling, and cardiac dysfunction. Metabolic alterations, increased inflammation, and imbalance of protein homeostasis contribute to the progression of this multifactorial syndrome, ultimately resulting in heart failure and death. Cancer-induced cardiac cachexia is associated with decreased quality of life, increased fatiguability, and decreased tolerance to therapeutic interventions.

Recent advances: While molecular mechanisms of this disease are not fully understood, researchers have identified different stages of progression of this disease, as well as potential biomarkers to detect and monitor the development. Preclinical and clinical studies have shown positive results when implementing certain pharmacological and non-pharmacological therapy interventions.

Critical issues: There are still no clear diagnostic criteria for cancer-mediated cardiac cachexia and the condition remains untreated, leaving cancer patients with irreversible effects of this syndrome. While traditional cardiovascular therapy interventions, such as beta-blockers, have shown some positive results in preclinical and clinical research studies, recent preclinical studies have shown more successful results with certain non-traditional treatment options that have not been further evaluated yet. There is still no clinical standard of care or approved FDA drug to aid in the prevention or treatment of cancer-induced cardiac cachexia. This review aims to revisit the still not fully understood pathophysiological mechanisms of cancer-induced cardiac cachexia and explore recent studies using novel treatment strategies.

Future directions: While research has progressed, further investigations might provide novel diagnostic techniques, potential biomarkers to monitor the progression of the disease, as well as viable pharmacological and non-pharmacological treatment options to increase quality of life and reduce cancer-induced cardiac cachexia-related mortality.

Keywords: cachexia; cancer; cardiac cachexia; heart; muscle wasting.