Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia (original) (raw)
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Differentiating Sarcopenia and Cachexia Among Patients With Cancer
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2017
Patients with cancer are at an increased risk for muscle loss via 2 distinct mechanisms: sarcopenia, defined as the age-associated decrease in muscle mass related to changes in muscle synthesis signaling pathways, and/or cachexia, defined as cytokine-mediated degradation of muscle and adipose depots. Both wasting disorders are prevalent; among patients with cancer, 15%-50% are sarcopenic and 25%-80% are cachectic. Muscle mass may be difficult to quantify in overweight/obese individuals. Often, overweight/obese patients with cancer are assumed to be normally nourished when in fact severe muscle depletion may be present. No universally accepted treatment exists for preventing or reversing sarcopenia or cachexia in patients with cancer. Current treatment options are limited to nutrition therapy and exercise, which may lead to difficulties in adherence during cancer treatment. Future treatments may provide pharmaceutical therapy that targets muscle degradation and synthesis pathways. Th...
Revisiting Cancer Cachexia: Pathogenesis, Diagnosis, and Current Treatment Approaches
2021
The objective of this article is to group together various management strategies and to highlight the recent treatment modifications that attempt to target the multimodal etiological factors involved in cancer cachexia. The contemporary role of nursing fraternity in psychosocial and nutritional assessment of cancer patients is briefly discussed. Cachexia is a syndrome of metabolic disturbance, characterized by the inflammation and loss of muscle with or without loss of adipose tissue. In cancer cachexia, a multifaceted condition, patients suffer from loss of body weight that leads to a negative impact on the quality of life and survival of the patients. The main cancers associated with cachexia are that of pancreas, stomach, lung, esophagus, liver, and that of bowel. The changes include increased proteolysis, lipolysis, insulin resistance, high energy expenditure, and reduced intake of food, all leading to impaired response to different treatments. There is no standardized treatment...
Physiological Reviews, 2009
I. Introduction 382 II. Energy Balance in Cachexia 382 A. Anorexia 383 B. Causes of anorexia: role of neuropeptides 384 C. Energy expenditure 384 D. Role of futile cycles 385 III. Adipose Tissue 386 A. Normal control of lipogenesis and lipolysis 386 B. Changes in adipose tissue in cachexia 387 IV. Tumor and Host Factors Influencing Adipose Mass in Cachexia 387 A. Lipid mobilizing factor/zinc ␣ 2-glycoprotein 387 B. Tumor necrosis factor-␣ 389 C. Interleukins 1 and 6 and interferon-␥ 390 V. Skeletal Muscle 391 A. Control of protein synthesis in normal and cachectic states 391 B. Protein degradation in cachexia 392 C. Apoptosis in skeletal muscle 394 VI. Tumor and Host Factors Influencing Muscle Mass in Cachexia 394 A. Proteolysis-inducing factor 394 B. Glucocorticoids 397 C. Tumor necrosis factor-␣ 398 D. Interleukin-6 399 E. Angiotensin II 399 VII. Treatment of Cachexia 400 A. Agents affecting appetite 400 B. Agents affecting cachectic mediators or signaling pathways 401 VII. Conclusions 402
Abstracts of the cancer cachexia conference, Boston, USA, 21-23 september 2012
Journal of cachexia, sarcopenia and muscle, 2012
Obesity and high-fat diet (HFD) are risk factors for multiple types of cancer. Compelling evidence indicates that obesity and diet also play a role after the diagnosis of cancer, influencing treatment, tumor progression, overall well-being and survival. Previously we reported that obesity is associated with increased overall survival in lung cancer patients. Others have shown that HFD was protective in murine MAC16 cachexia. Based on those data and similar obesity risk paradox observations in other diseases, we posited that obesity or HFD might provide increased physiological reserve and slow cachexia in cancer. Here we sought to determine whether diet induced obesity (DIO) or HFD were protective in the Lewis Lung carcinoma mouse model of cancer cachexia. DIO obese and C57Bl/6J lean mice were fed a HFD (60 %kcal from fat), while another lean group was fed normal chow (LFD) (10 %kcal from fat). Mice were inoculated with tumor cells and euthanized 17 and 23 days later. Both obese and lean tumor-bearing mice fed HFD showed increased loss of total body mass, skeletal muscle and fat mass compared with tumor-bearing mice fed LFD. This increased muscle wasting in DIO and HFD mice was associated with greatly reduced plasma insulin and adiponectin levels and increased levels of proinflammatory cytokines IL-6 and LIF versus LFD tumor-bearing controls. In DIO mice, plasma growth factor/cytokine changes corresponded to decreased muscle pAKT and pFOXO3a, and increased pSTAT3 levels, while pSMAD2 and NF-kB levels were unchanged. Taken together, these changes would inhibit anabolism, promote catabolism and drive the inflammatory phenotype, thus contributing to enhanced muscle wasting. In conclusion, our data suggest that both obesity, as a pre-existing condition, and high-fat diet consumption result in worsening of muscle wasting induced by tumor. Furthermore, neither increased body mass nor HFD were protective in experimental cancer cachexia.
Cachexia is considered as a complex interplay of metabolic and behavioral parameters leading to deteriorated quality of life. In recent years many efforts by researchers and clinicians were made to improve our knowledge of cachexia. Cancer and many other chronic or end-stage diseases like AIDS, chronic obstructive pulmonary disease, rheumatoid arthritis, tuberculosis are associated with cachexia, a condition associated with weight loss and alteration in body composition. Cachexia in cancer is generally neglected and contributes to the poor prognosis. A more meticulous understanding of cachexia is needed that probably will lead to combination therapies being developed. Although its prevalence is less, it is a growing problem in Asia. This review is based on the computer-aided Pubmed database and general search for the term “cancer cachexia”. Available free articles related to the pathophysiology, diagnosis and possible treatment modalities in cancer cachexia were downloaded for the review.
Cancer cachexia is defined by an ongoing loss of skeletal muscle mass
Annals of Palliative Medicine
Since 2007, a quantitative, specific and precise approach to the detection of muscle loss has become accessible with the advent of image-based assessments. Computed tomography images acquired as part of standard cancer care are the serendipitous substrate for these analyses. Three radiologicallydetermined abnormalities, sarcopenia (severe muscle depletion), catabolic loss of muscle over time, and reduced muscle radiation attenuation associate with progressive functional impairment, treatment-related complications, reduced quality of life, and mortality. Fundamental understanding of muscle wasting in cancer cachexia has been developed on a base of clinical and experimental studies, which have identified alterations in muscle protein synthesis, autophagy and ubiquitin-mediated proteolysis as key contributors to muscle loss. The etiology of cancer-associated muscle wasting is multifactorial. Tumor metabolism captures energy fuels and amino acids, and a suite of tumor-derived molecules elicits catabolic pathways at the tissue level in muscle. Endocrine, neural and inflammatory derangements add further catabolic drive. Antineoplastic agents make a substantial contribution to muscle wasting by directly action on muscle cells, as well as secondarily via their systemic side effects. Encouraging data is emerging as to the potential reversibility of muscle loss and/ or reduced muscle radiation attenuation through modulation of specific mechanisms. In the first line, pain and symptom management is a key element of the prevention of catabolic loss of muscle. Intake of intake of high-quality proteins and ω-3 polyunsaturated fatty acids support retention or gain of muscle mass. While there is no approved drug therapy for the indication of cancer-associated muscle wasting, there is preliminary evidence for robust gain of skeletal muscle mass in research studies of new therapeutics including inhibitors of mitogen-activated protein kinase kinases and ghrelin receptor agonists.
Definition and classification of cancer cachexia: an international consensus
The lancet oncology, 2011
To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia...
Cancer cachexia: understanding the molecular basis
Nature Reviews Cancer, 2014
| Cancer cachexia is a devastating, multifactorial and often irreversible syndrome that affects around 50-80% of cancer patients, depending on the tumour type, and that leads to substantial weight loss, primarily from loss of skeletal muscle and body fat. Since cachexia may account for up to 20% of cancer deaths, understanding the underlying molecular mechanisms is essential. The occurrence of cachexia in cancer patients is dependent on the patient response to tumour progression, including the activation of the inflammatory response and energetic inefficiency involving the mitochondria. Interestingly, crosstalk between different cell types ultimately seems to result in muscle wasting. Some of the recent progress in understanding the molecular mechanisms of cachexia may lead to new therapeutic approaches.
Emerging markers of cancer cachexia and their relationship to sarcopenia
Journal of Cancer Research and Clinical Oncology
Purpose Emerging biomarkers of cancer cachexia and their roles in sarcopenia and prognosis are poorly understood. Baseline assessments of anthropometrics, sarcopenia, cachexia status and biomarkers of cachexia were measured in patients with advanced cancer and healthy controls. Thereafter, relationships of the biomarkers with cachexia and sarcopenia were explored. Methods A prospective case–control design was used, including 40 patients with advanced cancer and 40 gender, age-matched controls. Bioelectrical impedance [skeletal muscle index (SMI)] and hand dynamometry [hand grip strength (HGS)] assessed sarcopenia and a validated tool classified cancer cachexia. Albumin, lymphocyte and platelet counts, haemoglobin, C-reactive protein (CRP), pro-inflammatory cytokines/chemokines and citrullinated histone H3 (H3Cit) were measured. Results Patients had significantly lower SMI (6.67 kg/m2 versus 7.67 kg/m2, p = < 0.01) and HGS (24.42 kg versus 29.62 kg) compared to controls, with 43%...