Advancing the Understanding and Treatment of Cancer Cachexia: Mechanisms, Therapeutic Approaches, and Future Opportunities

Abstract

Cancer cachexia (CC) is a prevalent metabolic disorder in patients with advanced cancer, characterized by persistent skeletal muscle mass loss and irreversible body weight reduction, which significantly diminishes quality of living, therapeutic effectiveness. At present, the specific pathogenesis of CC is only defined as skeletal muscle loss induced by signaling pathways. In the clinical treatment of tumor cachexia, it has been clearly defined that there are multiple methods available for treating this disease, including nutritional therapy and exercise, but all of them have very little therapeutic effect. Surprisingly, traditional Chinese medicine has achieved initial success in treating malignant tumors, and the combined treatment of traditional Chinese and Western medicine has yielded remarkable results. Therefore, it is an urgent need to elucidate the more specific pathogenesis of CC to develop effective treatment approaches, which enhance patients' nutritional health status as well as their overall quality of life and survival ratings. This article aims to review the pathogenesis of CC along with clinical treatment strategies and drug utilization.

Keywords: Traditional Chinese medicine; cachexia; cancer; mechanism; nutrition; treatment.

Figure 1

Various organs are involved in the development of CC. The relationship between CC and adipose tissue, liver, brain and other organs is shown in the figure, in which inflammatory cytokines play a major role and connect various organs. Both systemic inflammatory responses and tumor cells can promote the secretion of inflammatory cytokines. These inflammatory factors transmit information to the stomach, causing intestinal malabsorption, intestinal barrier dysfunction and intestinal endotoxemia. The stomach and adipose tissue respectively release polypeptides and leptin, which send signals to the brain and promote the occurrence of anorexia. Inflammatory factors can also directly stimulate adipose tissue to promote the production of brown fat and generate heat. Inflammatory factors carry out the Cori cycle in part of the liver and promote protein synthesis and degradation in the skeletal muscle part of the heart.

Figure 2

The developmental stage of CC. With the development of CC, the weight of patient decreases, food intaking degrades, and survival time diminishes gradually.In the early stage of cachexia, the body undergoes a series of metabolic changes, and there is a certain possibility of anorexia and weight loss. During the cachexia stage, the body will develop systemic inflammation. At this time, the patient’s food intake decreases and their weight drops by greater than 5%. During the refractory cachexia stage, patients have failed multiple times with anti-cancer drugs, and at this point, their survival period is less than three months.

Figure 3

The JAK/STAT3 pathway regulates muscle atrophy. JAK/STAT3 signaling pathway has a regulatory effect on the ubiquitin proteasome pathway and autophagy pathway, causes skeletal muscle atrophy by regulating both pathways.