Journal
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
Volume 45, Issue -, Pages 16-25Publisher
WILEY
DOI: 10.1002/jpen.2287
Keywords
animal models; anorexia; appetite; cachexia; cancer; malnutrition; nutrition
Categories
Funding
- U.S. Department ofVeterans Affairs [I01BX004177, I01CX002046]
- National Cancer Institute [P01CA236778, P30CA082709]
- National Institute of General Medical Sciences [R01GM137656]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [P30AR072581]
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Cancer cachexia is a complex syndrome involving metabolic changes and wasting of peripheral tissues, with challenges in defining appropriate nutrition interventions and lack of effective therapies. The influence of tumors on neural mechanisms and the need for multimodal interventions are highlighted, along with the increasing efforts in diagnosing and staging cachexia. Despite differences in treatment recommendations, clinical trial activity and preclinical models continue to evolve for a better understanding and management of cancer cachexia.
Cancer cachexia, or progressive weight loss, often despite adequate nutrition contributes greatly to cancer morbidity and mortality. Cachexia is metabolically distinct from starvation or protein malnutrition, although many patients with cancer and cachexia exhibit lowered appetite and food consumption. Tumors affect neural mechanisms that regulate appetite and energy expenditure, while promoting wasting of peripheral tissues via catabolism of cardiac and skeletal muscle, adipose, and bone. These multimodal actions of tumors on the host suggest a need for multimodal interventions. However, multiple recent consensus guidelines for management of cancer cachexia differ in treatment recommendations, highlighting the lack of effective, available therapies. Challenges to defining appropriate nutrition or other interventions for cancer cachexia include lack of consensus on definitions, low strength of evidence from clinical trials, and a scarcity of robust, rigorous, and mechanistic studies. However, efforts to diagnose, stage, and monitor cachexia are increasing along with clinical trial activity. Furthermore, preclinical models for cancer cachexia are growing more sophisticated, encompassing a greater number of tumor types in organ-appropriate contexts and for metastatic disease to model the clinical condition more accurately. It is expected that continued growth, investment, and coordination of research in this topic will ultimately yield robust biomarkers, clinically useful classification and staging algorithms, targetable pathways, pivotal clinical trials, and ultimately, cures. Here, we provide an overview of the clinical and scientific knowledge and its limitations around cancer cachexia.
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