Cancer cachexia, recent advances, and future directions

Abstract

Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass with or without loss of fat mass. The syndrome cannot be fully reversed by conventional nutritional support, and despite an increased number of studies related to cancer cachexia, the underlying mechanisms are still poorly defined, and therapeutic options are limited. This review focuses on recent studies investigating mechanisms and pathways in cancer cachexia. The role of molecular and functional imaging in identifying cachexia at an earlier stage, in identifying potential metabolic targets and pathways, and in assessing treatment efficacy is also reviewed.

Figures

Figure 1

(A) Three stages of the cachectic syndrome and corresponding diagnostic criteria. Adapted with permission from [1]. (B) Pathogenesis of cancer cachexia.

Figure 2

Representative CT images and tissue areas: (A) placebo crossed over to Sorafenib. (B) Sorafenib at 6 months and 1 year, showing loss of muscle (red) after initiation of Sorafenib and loss of subcutaneous (blue) and visceral (yellow) adipose tissue in the long-term Sorafenib-treated patient. Adapted with permission from [29].

Figure 3

(A) Representative PET images of 18FDG uptake in MAC13 and MAC16 tumor bearing mice (SUV: standardized uptake value). (B) Quantification of the uptake in the tumors. Values represent Mean ± SEM (MAC13, n = 8, MAC16, n = 5; * P < 0.005). Adapted with permission from [34].

Figure 4

(A) Cross-sectional T1-weighted images, (B) cross-sectional lactate+lipids maps, and (C) merged images from (A) and (B) of MAC13 (upper panel) and MAC16 (lower panel) tumor-bearing mice. T1-weighted images were acquired from the corresponding 4 mm slice used for MRSI using a spin-echo sequence with an echo time of 10 ms, a repetition time of 500 ms, and an in-plane spatial resolution of 125 µm. Lipid maps were generated from MRSI data and normalized to the water signal. Volumes were comparable for the MAC13 (540 mm3) and MAC16 (545 mm3) tumors. Adapted with permission from [34].