1.
Cancer Cachexia and Related Metabolic Dysfunction.
Fonseca, GWPD, Farkas, J, Dora, E, von Haehling, S, Lainscak, M
International journal of molecular sciences. 2020;(7)
Abstract
Cancer cachexia is a complex multifactorial syndrome marked by a continuous depletion of skeletal muscle mass associated, in some cases, with a reduction in fat mass. It is irreversible by nutritional support alone and affects up to 74% of patients with cancer-dependent on the underlying type of cancer-and is associated with physical function impairment, reduced response to cancer-related therapy, and higher mortality. Organs, like muscle, adipose tissue, and liver, play an important role in the progression of cancer cachexia by exacerbating the pro- and anti-inflammatory response initially activated by the tumor and the immune system of the host. Moreover, this metabolic dysfunction is produced by alterations in glucose, lipids, and protein metabolism that, when maintained chronically, may lead to the loss of skeletal muscle and adipose tissue. Although a couple of drugs have yielded positive results in increasing lean body mass with limited impact on physical function, a single therapy has not lead to effective treatment of this condition. Therefore, a multimodal intervention, including pharmacological agents, nutritional support, and physical exercise, may be a reasonable approach for future studies to better understand and prevent the wasting of body compartments in patients with cancer cachexia.
2.
Medical Cannabinoids for Cancer Cachexia: A Systematic Review and Meta-Analysis.
Wang, J, Wang, Y, Tong, M, Pan, H, Li, D
BioMed research international. 2019;:2864384
Abstract
OBJECTIVES Cancer cachexia (CCA) is an intractable and ineffective metabolic syndrome that attacks 50-80% of cancer patients. It reduces patient's life quality, affects the efficacy of treatment, and then increases their mortality; however, there are no established therapeutic strategies for CCA in the world. In this study, we assess the positive and negative effects of cannabinoid in the treatment of CCA. METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Web of Science, and PubMed up to December 2017. RESULTS Of the 256 screened studies, three studies with a total of 592 participants were included. Compared with placebo, cannabinoid increased the appetite (MD 0.27, 95% CI -0.51 to 1.04; n= 3) but failed to improve the overall quality of life (QOL; MD -12.39, 95% CI [-24.21 to -0.57; n = 2), and a total of 441 patients had 607 adverse events (AEs; 496 in the cannabinoid group and 111 in the placebo group). CONCLUSIONS Our analysis showed cannabinoid is effective in increasing appetite in cancer patients. However, it declines the quality of life, which may be due to the side effects of cannabinoid.
3.
Cachexia Anorexia Syndrome and Associated Metabolic Dysfunction in Peritoneal Metastasis.
Archid, R, Solass, W, Tempfer, C, Königsrainer, A, Adolph, M, Reymond, MA, Wilson, RB
International journal of molecular sciences. 2019;(21)
Abstract
: Patients with peritoneal metastasis (PM) of gastrointestinal and gynecological origin present with a nutritional deficit characterized by increased resting energy expenditure (REE), loss of muscle mass, and protein catabolism. Progression of peritoneal metastasis, as with other advanced malignancies, is associated with cancer cachexia anorexia syndrome (CAS), involving poor appetite (anorexia), involuntary weight loss, and chronic inflammation. Eventual causes of mortality include dysfunctional metabolism and energy store exhaustion. Etiology of CAS in PM patients is multifactorial including tumor growth, host response, cytokine release, systemic inflammation, proteolysis, lipolysis, malignant small bowel obstruction, ascites, and gastrointestinal side effects of drug therapy (chemotherapy, opioids). Metabolic changes of CAS in PM relate more to a systemic inflammatory response than an adaptation to starvation. Metabolic reprogramming is required for cancer cells shed into the peritoneal cavity to resist anoikis (i.e., programmed cell death). Profound changes in hexokinase metabolism are needed to compensate ineffective oxidative phosphorylation in mitochondria. During the development of PM, hypoxia inducible factor-1α (HIF-1α) plays a key role in activating both aerobic and anaerobic glycolysis, increasing the uptake of glucose, lipid, and glutamine into cancer cells. HIF-1α upregulates hexokinase II, phosphoglycerate kinase 1 (PGK1), pyruvate dehydrogenase kinase (PDK), pyruvate kinase muscle isoenzyme 2 (PKM2), lactate dehydrogenase (LDH) and glucose transporters (GLUT) and promotes cytoplasmic glycolysis. HIF-1α also stimulates the utilization of glutamine and fatty acids as alternative energy substrates. Cancer cells in the peritoneal cavity interact with cancer-associated fibroblasts and adipocytes to meet metabolic demands and incorporate autophagy products for growth. Therapy of CAS in PM is challenging. Optimal nutritional intake alone including total parenteral nutrition is unable to reverse CAS. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) stabilized nutritional status in a significant proportion of PM patients. Agents targeting the mechanisms of CAS are under development.