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Expert Opinion on Pharmacotherapy Apr 2023Cancer cachexia is a multifactorial metabolic syndrome associated with a pathophysiology intertwined with increased inflammatory response, anorexia, metabolic... (Review)
Review
INTRODUCTION
Cancer cachexia is a multifactorial metabolic syndrome associated with a pathophysiology intertwined with increased inflammatory response, anorexia, metabolic dysregulation, insulin resistance, and hormonal alterations, which together generate a negative energy balance in favor of catabolism. The development of therapeutic strategies to treat cancer cachexia has always been related to clinical interventions with increased food intake/supplementation, physical exercise regimens, and/or medication to attenuate catabolism and increase the anabolic response. However, the approval of drugs by regulatory agencies has always been a challenge.
AREAS COVERED
This review outlines the main pharmacotherapy findings in cancer cachexia as well as the ongoing clinical trials that have evaluated changes in body composition and muscle function. The National Library of Medicine (PubMed) was used as search tool.
EXPERT OPINION
The pharmacological therapy for cachexia should be focused on improving body composition, muscle function, and mortality, although none of the compounds used so far was able to demonstrate positive results beyond increased appetite and improvements in body composition. Ponsegromab (GDF15 inhibitor), a new compound that has just entered a phase II clinical trial, is a promising candidate to treat cancer cachexia and may produce exciting results if the study can be conducted as planned.
Topics: Humans; Cachexia; Neoplasms; Insulin Resistance; Anorexia
PubMed: 36995115
DOI: 10.1080/14656566.2023.2194489 -
CNS Neuroscience & Therapeutics Dec 2022Immunological dysfunctions in eating disorders have recently gained increasing scientific attention. Furthermore, the reciprocal association between anorexia and... (Review)
Review
Immunological dysfunctions in eating disorders have recently gained increasing scientific attention. Furthermore, the reciprocal association between anorexia and autoimmune diseases is of particular interest and suggests a role of autoimmunity in the pathogenesis of eating disorders. Anorexia nervosa (AN) and autoimmune diseases are linked by a bidirectional relationship based on common immunopathological mechanisms. In this review, in addition to reporting the numerous cases described in which autoimmune disorders are associated with anorexia or vice versa, we summarize the many aspects of this relationship between the immune system (IS) and AN. We describe how the microbiota affects the IS, disrupts gut-brain communication, and possibly triggers eating disorders. We also describe the shared immunological pathways of autoimmune and eating disorders and in particular the occurrence of disrupted T cell tolerance and autoantibodies in AN. The described observations represent the starting point for possible, future research directions.
Topics: Humans; Anorexia Nervosa; Anorexia; Feeding and Eating Disorders; Comorbidity; Autoimmune Diseases
PubMed: 36114699
DOI: 10.1111/cns.13953 -
Journal of Cachexia, Sarcopenia and... Apr 2019Cachexia is a complex metabolic process that is associated with several end-stage organ diseases. It is known to be also associated with advanced dementia, although the... (Review)
Review
Cachexia is a complex metabolic process that is associated with several end-stage organ diseases. It is known to be also associated with advanced dementia, although the pathophysiologic mechanisms are still largely unknown. The present narrative review is aimed at presenting recent insights concerning the pathophysiology of weight loss and wasting syndrome in dementia, the putative mechanisms involved in the dysregulation of energy balance, and the interplay among the chronic clinical conditions of sarcopenia, malnutrition, and frailty in the elderly. We discuss the clinical implications of these new insights, with particular attention to the challenging question of nutritional needs in advanced dementia and the utility of tube feeding in order to optimize the management of end-stage dementia.
Topics: Aging; Anorexia; Cachexia; Dementia; Disease Susceptibility; Frailty; Humans; Sarcopenia; Translational Research, Biomedical
PubMed: 30794350
DOI: 10.1002/jcsm.12380 -
The Biochemical Journal Jul 2017Anorexia and metabolic alterations are the main components of the cachectic syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other alterations... (Review)
Review
Anorexia and metabolic alterations are the main components of the cachectic syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other alterations are involved in the development of cancer cachexia, a multi-organ syndrome. Nutritional approach strategies are not satisfactory in reversing the cachectic syndrome. The aim of the present review is to deal with the recent therapeutic targeted approaches that have been designed to fight and counteract wasting in cancer patients. Indeed, some promising targeted therapeutic approaches include ghrelin agonists, selective androgen receptor agonists, β-blockers and antimyostatin peptides. However, a multi-targeted approach seems absolutely essential to treat patients affected by cancer cachexia. This approach should not only involve combinations of drugs but also nutrition and an adequate program of physical exercise, factors that may lead to a synergy, essential to overcome the syndrome. This may efficiently reverse the metabolic changes described above and, at the same time, ameliorate the anorexia. Defining this therapeutic combination of drugs/nutrients/exercise is an exciting project that will stimulate many scientific efforts. Other aspects that will, no doubt, be very important for successful treatment of cancer wasting will be an optimized design of future clinical trials, together with a protocol for staging cancer patients in relation to their degree of cachexia. This will permit that nutritional/metabolic/pharmacological support can be started early in the course of the disease, before severe weight loss occurs. Indeed, timing is crucial and has to be taken very seriously when applying the therapeutic approach.
Topics: Adrenergic beta-Antagonists; Androgen Receptor Antagonists; Anorexia; Cachexia; Diet Therapy; Exercise Therapy; Ghrelin; Humans; Myostatin; Neoplasms; Peptides
PubMed: 28751550
DOI: 10.1042/BCJ20170032 -
The Journal of Nutrition, Health & Aging 2023
Topics: Humans; Anorexia; Aging
PubMed: 36973923
DOI: 10.1007/s12603-023-1899-1 -
Clinics in Geriatric Medicine Aug 2017Older people often experience loss of appetite and/or decreased food intake that, unavoidably, impact energy metabolism and overall health status. The association of... (Review)
Review
Older people often experience loss of appetite and/or decreased food intake that, unavoidably, impact energy metabolism and overall health status. The association of age-related nutritional deficits with several adverse outcomes has led to the recognition of a geriatric condition referred to as "anorexia of aging." Anorexia is an independent predictor of morbidity and mortality both in the community and across clinical settings. Multidimensional interventions within personalized care plans currently represent the most effective option to ensure the provision of adequate amounts of food, limit weight loss, and prevent adverse health outcomes in older adults.
Topics: Aged; Aging; Anorexia; Disease Management; Geriatric Assessment; Humans; Nutritional Status
PubMed: 28689565
DOI: 10.1016/j.cger.2017.02.004 -
The Biochemical Journal May 2021Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in... (Review)
Review
Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis. Therefore, the lack of definitive therapeutic strategies for cancer cachexia emphasizes the need to develop a better understanding of the underlying mechanisms. Increasing evidences show that the progression of cachexia is associated with metabolic alternations, which mainly include excessive energy expenditure, increased proteolysis and mitochondrial dysfunction. In this review, we provided an overview of the key mechanisms of cancer cachexia, with a major focus on muscle atrophy, adipose tissue wasting, anorexia and fatigue and updated the latest progress of pharmacological management of cancer cachexia, thereby further advancing the interventions that can counteract cancer cachexia.
Topics: Adipose Tissue; Anorexia; Anti-Inflammatory Agents; Antineoplastic Agents; Appetite Stimulants; Cachexia; Fatigue; Humans; Mitochondria; Muscle, Skeletal; Muscular Atrophy; Neoplasms; Quality of Life; Survival Analysis; Testosterone Congeners; Weight Loss
PubMed: 33970218
DOI: 10.1042/BCJ20201009 -
Peptides Oct 2015The rapid aging of the world's population has led to a need to increase our understanding of the pathophysiology of the factors leading to frailty and cognitive decline.... (Review)
Review
The rapid aging of the world's population has led to a need to increase our understanding of the pathophysiology of the factors leading to frailty and cognitive decline. Peptides have been shown to be involved in the pathophysiology of frailty and cognitive decline. Weight loss is a major component of frailty. In this review, we demonstrate a central role for both peripheral peptides (e.g., cholecystokinin and ghrelin) and neuropeptides (e.g., dynorphin and alpha-MSH) in the pathophysiology of the anorexia of aging. Similarly, peripheral peptides (e.g., ghrelin, glucagon-like peptide 1, and cholecystokinin) are modulators of memory. A number of centrally acting neuropeptides have also been shown to modulate cognitive processes. Amyloid-beta peptide in physiological levels is a memory enhancer, while in high (pathological) levels, it plays a key role in the development of Alzheimer's disease.
Topics: Aging; Animals; Anorexia; Cognition; Humans; Memory; Peptide Hormones
PubMed: 25895851
DOI: 10.1016/j.peptides.2015.04.007 -
Experimental & Molecular Medicine Apr 2022Cancer cachexia syndrome is a major cause of morbidity and mortality in cancer patients in the advanced stage. It is a devastating disorder characterized by nutritional... (Review)
Review
Cancer cachexia syndrome is a major cause of morbidity and mortality in cancer patients in the advanced stage. It is a devastating disorder characterized by nutritional impairment, weakness, and wasting, and it affects treatment success and quality of life. Two major symptoms of cancer cachexia are anorexia and weight loss. Weight loss in cachexia is not reversed through increased food intake, suggesting that anorexia and weight loss in cancer patients are regulated by independent molecular mechanisms. Although the wasting phenotype mostly occurs in skeletal muscle and adipose tissue, other organs, such as the brain, liver, pancreas, heart, and gut, are also involved in cachexia. Thus, cachexia is a multiorgan syndrome. Although the molecular basis of cancer cachexia-induced weight loss is known, the mechanism underlying anorexia is poorly understood. Here, we highlight our recent discovery of a new anorexia mechanism by which a tumor-derived humoral factor induces cancer anorexia by regulating feeding-related neuropeptide hormones in the brain. Furthermore, we elucidated the process through which anorexia precedes tissue wasting in cachexia. This review article aims to provide an overview of the key molecular mechanisms of anorexia and tissue wasting caused by cancer cachexia.
Topics: Adipose Tissue; Anorexia; Cachexia; Humans; Neoplasms; Quality of Life
PubMed: 35388147
DOI: 10.1038/s12276-022-00752-w -
Nutrients Jun 2023Anorexia of aging is a common problem in older adults. Depending on the setting, its prevalence varies from about 10% (among community-dwelling older adults) to over 30%... (Review)
Review
Anorexia of aging is a common problem in older adults. Depending on the setting, its prevalence varies from about 10% (among community-dwelling older adults) to over 30% in acute wards and nursing homes. The objective of this systematic review was to establish the prevalence of poor appetite in frail persons ≥60 years of age. We performed a literature search for studies where the prevalence of anorexia of aging among frail and pre-frail old adults was reported. 957 articles on this topic were identified. After eligibility assessment, three articles were included in the review. The studies included 4657 community-dwelling older adults. The weighted total prevalence of anorexia of aging in all the included studies was 11.3%. Among frail and pre-frail participants, loss of appetite was reported in 20.5% (weighted estimate). Overall, robust status was associated with a 63% lower probability of concomitant anorexia of ageing (OR 0.37, 95%CI 0.21-0.65, = 0.0005). Frailty or risk of frailty are associated with more prevalent anorexia of ageing. This has potential practical implications; however, more research, especially to elucidate the direction of the relation, is needed.
Topics: Humans; Aged; Aged, 80 and over; Frailty; Frail Elderly; Anorexia; Appetite; Aging; Geriatric Assessment
PubMed: 37447292
DOI: 10.3390/nu15132966