Lung Cancer Cachexia: Can Molecular Understanding Guide Clinical Management?

Abstract

Cachexia has been recognized for a long time as an adverse effect of cancer. It is associated with reduced physical function, reduced tolerance to anticancer therapy, and reduced survival. This wasting syndrome is mainly known for an ongoing loss of skeletal muscle leading to progressive functional impairment and is driven by a variable combination of reduced food intake and abnormal metabolism. Cytokines derived from host immune system or the tumor itself is believed to play a role in promoting cancer cachexia. Circulating levels of cytokines, including IL-1α, IL-6, and TNFα have been identified in cancer patients but they probably only represent a small part of a changed and abnormal metabolism. Murine models have shown that browning of white adipose tissue (WAT) takes place early in the progression of cancer cachexia. Thus, browning of white adipose tissue is believed to be a strong contributor to the increased energy expenditure common in cachectic patients. Despite the severe implications of cancer cachexia for the patients and extensive research efforts, a more coherent and mechanistic explanation of the syndrome is lacking, and for many clinicians, cancer cachexia is still a vague concept. From a lung cancer perspective this commentary reviews the current knowledge on cancer cachexia mechanisms and identifies specific ways of clinical management regarding food intake, systemic inflammation, and muscular dysfunction. Much of what we know comes from preclinical studies. More translational research is needed for a future cancer cachexia screening tool to guide clinicians, and here possible variables for a cancer cachexia screening tool are considered.

Keywords: browning of adipose tissue; cancer cachexia; clinical management; cytokines; inflammation; lung cancer; mechanisms; molecular; screening tool; weight loss.

Figure 1.

Warning symptoms: When a cancer patient presents with these symptoms consider cancer cachexia.

Figure 2.

No single fixer-drug for a multidimensional syndrome. Target the underlying cancer if possible, alleviate secondary nutrition impact symptoms, and stimulate physical training.

Figure 3.

Possible variables to incorporate in a future cancer cachexia screening tool.