Cancer Cachexia: Mediators, Signaling, and Metabolic Pathways

Fearon, Kenneth C. H.; Glass, David J.; Guttridge, Denis C.

doi:10.1016/j.cmet.2012.06.011

Cited by 1,030 publications

(1,130 citation statements)

References 178 publications

(202 reference statements)

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“…Recent studies suggest the dysregulation of inflammatory cytokines cause and intensify CRF and its related symptoms. 11,12,[57][58][59] In our study, 63% of the patients perceived moderate to vast improvement of improvement in CRF with PG treatment.…”

Section: Discussionmentioning

confidence: 91%

High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue

et al. 2015

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Introduction and Objective. Cancer-related fatigue (CRF) is the most common and severe symptom in patients with cancer. The number and efficacy of available treatments for CRF are limited. The objective of this preliminary study was to assess the safety of high-dose Panax ginseng (PG) for CRF. Methods. In this prospective, open-label study, 30 patients with CRF (≥4/10) received high-dose PG at 800 mg orally daily for 29 days. Frequency and type of side effects were determined by the National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 4.0. Scores on the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scale, Edmonton Symptom Assessment System (ESAS), and Hospital Anxiety and Depression Scale (HADS) were assessed at baseline, day 15, and day 29. Global Symptom Evaluation (GSE) was assessed at day 29. Results. Of the 30 patients enrolled, 24 (80%) were evaluable. The median age was 58 years; 50% were females, and 84% were white. No severe (≥grade 3) adverse events related to the study drug were reported. Of the 24 evaluable patients, 21 (87%) had an improved (by ≥3 points) FACIT-F score by day 15. The mean ESAS score (standard deviation) for well-being improved from 4.67 (2.04) to 3.50 (2.34) ( P = .01374), and mean score for appetite improved from 4.29 (2.79) to 2.96 (2.46) ( P = .0097). GSE score of PG for fatigue was ≥3 in 15/24 patients (63%) with median improvement of 5. Conclusion. PG is safe and improves CRF fatigue as well as overall quality of life, appetite, and sleep at night. Randomized controlled trials of PG for CRF are justified.

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Section: Discussionmentioning

confidence: 91%

High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue

et al. 2015

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“…One possible reason these therapies are unsuccessful in achieving long‐term survival is that they fail to treat cachexia, which is a key underlying cause of PDAC morbidity and mortality 10, 11, 12, 39. Even PDAC tumours of exceptionally small size are capable of inducing the widespread physiologic, metabolic, and behavioural changes that define cachexia 6, 33, 40. Therefore, PDAC is a critical priority in cachexia research, and more effort must be directed toward elucidating molecular mechanisms and therapeutic targets in PDAC cachexia.…”

Section: Discussionmentioning

confidence: 99%

“…Cachexia's impact extends beyond its widespread harm to quality of life, and it is estimated to be the direct cause of death in 20–30% of all cancer patients 3, 4. In addition, cachexia contributes to cancer‐associated morbidity by weakening patients to the point they cannot tolerate chemotherapy or surgery 5, 6, 7. Despite the widespread need for improved cachexia therapies, there remain very few treatments for this condition 8, 9.…”

Section: Introductionmentioning

confidence: 99%

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

Michaelis

Zhu

Burfeind

et al. 2017

J cachexia sarcopenia muscle

120

161

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BackgroundCachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC‐associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRASG12D P53R172H Pdx‐Cre+/+ (KPC) mouse.MethodsMale and female C57BL/6 mice were inoculated subcutaneously, intraperitoneally, or orthotopically with KPC tumour cells. We performed rigorous phenotypic, metabolic, and behavioural analysis of animals over the course of tumour development.ResultsAll routes of administration produced rapidly growing tumours histologically consistent with moderate to poorly differentiated PDAC. The phenotype of this model was dependent on route of administration, with orthotopic and intraperitoneal implantation inducing more severe cachexia than subcutaneous implantation. KPC tumour growth decreased food intake, decreased adiposity and lean body mass, and decreased locomotor activity. Muscle catabolism was observed in both skeletal and cardiac muscles, but the dominant catabolic pathway differed between these tissues. The wasting syndrome in this model was accompanied by hypothalamic inflammation, progressively decreasing brown and white adipose tissue uncoupling protein 1 (Ucp1) expression, and increased peripheral inflammation. Haematological and endocrine abnormalities included neutrophil‐dominant leukocytosis and anaemia, and decreased serum testosterone.ConclusionsSyngeneic KPC allografts are a robust model for studying cachexia, which recapitulate key features of the PDAC disease process and induce a wide array of cachexia manifestations. This model is therefore ideally suited for future studies exploring the physiological systems involved in cachexia and for preclinical studies of novel therapies.

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“…Cancer cachexia is a muscle‐wasting syndrome, which affects up to 80% of advanced cancer patients and is considered to be responsible of 20% of all cancer deaths 1. Despite intense research, mechanisms of cachexia are still poorly characterized, and therapeutic targets are desperately lacking.…”

Section: Introductionmentioning

confidence: 99%

Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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BackgroundSeveral experimental evidences pinpoint the possible role of Activin A (ActA) as a driver of cancer cachexia. Supporting this hypothesis, we showed recently that human cancer cachexia is associated with high ActA levels. Moreover, ActA levels were correlated with body weight loss and skeletal muscle density, two prognostic factors in cancer patients. Our goal was therefore to investigate the value of ActA to predict survival in cancer patients.MethodsPatients with colorectal or lung cancer were prospectively enrolled at the time of diagnosis or relapse between January 2012 and March 2014. At baseline, patients had clinical, nutritional, and functional assessment. Body composition and skeletal muscle density were measured by CT scan, and plasma ActA concentrations were determined. Overall survival (OS) was analysed since inclusion to 24 months later.ResultsSurvival data were available for 149 patients out of 152. Patients with high ActA (≥408 pg/mL) had lower OS than those with low levels, regardless the type of cancer (OS in colorectal cancer, 50% vs. 79%, P < 0.05; and in lung cancer, 27% vs. 67%, P = 0.001). The multivariable analysis confirmed the prognostic value of ActA independently of tumour stage or inflammatory markers, particularly in lung cancer. Low muscularity was also an independent prognostic factor.ConclusionsOur study demonstrates that high ActA level is an independent prognosis factor of survival in cancer patients. More than a basic marker of the severity of the neoplastic disease or of the inflammatory process, ActA seems to influence survival by contributing to the development of cachexia and loss of skeletal muscle mass.

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Cancer Cachexia: Mediators, Signaling, and Metabolic Pathways

Cited by 1,030 publications

References 178 publications

High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue

High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

Circulating Activin A predicts survival in cancer patients

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