Cancer cachexia: biomarkers and the influence of age

Abstract

Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of cancer patients succumb directly to Ccx, yet therapies that effectively address this perturbed metabolic state are rare. In recent decades, several characteristics of Ccx have been established in mice and humans, of which we here highlight adipose tissue dysfunction, muscle wasting and systemic inflammation, as they are directly linked to biomarker discovery. To counteract cachexia pathogenesis as early as possible and mitigate its detrimental impact on anti-cancer treatments, identification and validation of clinically endorsed biomarkers assume paramount importance. Ageing was recently shown to affect both the validity of Ccx biomarkers and Ccx development, but the underlying mechanisms are still unknown. Thus, unravelling the intricate interplay between ageing and Ccx can help to counteract Ccx pathogenesis and tailor diagnostic and treatment strategies to individual needs.

Keywords: ageing; biomarker; cachexia; cancer; inflammation; metabolism.

Fig. 1

The interplay of cancer cachexia and ageing with a focus on biomarkers in disease progression. Factors released from tumour and different diseased tissues contribute to the pathogenesis of cachexia and metabolic dysfunction upon ageing, and can be used as biomarkers. The affected processes partially overlap. Abbreviations shown in abbreviation list.

Fig. 2

The three characteristics of cancer cachexia highlighted in the current review. Tumour‐ and host‐secreted factors induce adipose tissue wasting, skeletal muscle degradation and systemic inflammation through various molecular mechanisms. The combination of these effects negatively influences several aspects of patient health.

Fig. 3

Biomarkers in cancer cachexia. Shown are several cachexia markers, grouped according to the three characteristics of cachexia highlighted in the current review: adipose tissue wasting, skeletal muscle wasting and systemic inflammation. In addition, new indices and scores are shown, aiming to improve biomarker validity by integrating multiple biomarkers. Abbreviations shown in abbreviation list.

Fig. 4

Common pathways and circulating factors in cachexia and ageing. The aged population shows an increased risk of developing cancer and its accompanying syndrome cancer cachexia. Metabolic, genomic and behavioural alterations upon ageing increase the risk for cancer and Ccx development. Red arrows indicate changes in cachexia, blue/dotted arrows indicate changes in ageing. Abbreviations shown in abbreviation list.