The Nutritional Challenges of Cancer Cachexia

Abstract

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, though many patients with cancer and cachexia exhibit lowered appetite and food consumption. Tumors affect neural mechanisms regulating appetite and energy expenditure, while promoting wasting of peripheral tissues via catabolism of cardiac and skeletal muscle, adipose, and bone. These multi-modal actions of tumors on the host suggest a need for multi-modal 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 nutritional 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. As well, preclinical models for cancer cachexia are growing more sophisticated, encompassing a greater number of tumor types in organ-appropriate contexts and for metastatic disease in order 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.