Novel targeted therapies for cancer cachexia

2017 ◽  
Vol 474 (16) ◽  
pp. 2663-2678 ◽  
Author(s):  
Josep M. Argilés ◽  
Francisco Javier López-Soriano ◽  
Britta Stemmler ◽  
Sílvia Busquets

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.

Author(s):  
Josep M. Argilés ◽  
Francisco Javier López-Soriano ◽  
Britta Stemmler ◽  
Silvia Busquets

Cancer cachexia has two main components: anorexia and metabolic alterations. The main changes associated with the development of this multi-organic syndrome are glucose intolerance, fat depletion and muscle protein hypercatabolism. The aim of this paper is to review the more recent therapeutic approaches designed to counteract the wasting suffered by the cancer patient with cachexia. Among the most promising approaches we can include the use of ghrelin agonists, beta-blockers, beta-adrenergic agonists, androgen receptor agonists and anti-myostatin peptides. The multi-targeted approach seems essential in these treatments, which should include the combination of both nutritional support, drugs and a suitable program of physical exercise, in order to ameliorate both anorexia and the metabolic changes associated with cachexia. In addition, another very important and crucial aspect to be taken into consideration in the design of clinical trials for the treatment of cancer cachexia is to staging cancer patients in relation with the degree of cachexia, in order to start as early as possible this triple approach in the course of the disease, even before the weight loss can be detected.


1992 ◽  
Vol 216 (3) ◽  
pp. 280-290 ◽  
Author(s):  
RONALD F. WOLF ◽  
DAVID B. PEARLSTONE ◽  
ELLIOT NEWMAN ◽  
MARTIN J. HESLIN ◽  
AMNON GONENNE ◽  
...  

Author(s):  
Angelika Beirer

Summary Background The prevalence of malnutrition in cancer patients ranges from about 20% to more than 70%. However, 10–20% of cancer patients’ deaths are related to malnutrition, not the malignancy itself. To reverse the pattern of weight loss, improve the patients’ quality of life, reduce the treatment toxicity, the psychological stress and the risk of mortality, the diagnosis of malnutrition should be made as early as possible to facilitate the best possible treatment. Methods A systematic literature search was conducted following guidelines of ESPEN (European Society for Clinical Nutrition), DGEM (German Society for Nutritional Medicine) and ASPEN (American Society for Parenteral and Enteral Nutrition). Results and conclusion To assess the risk of malnutrition, all cancer patients should be screened regularly with a valid screening tool (e.g., MUST [Malnutrition Universal Screening Tool], NRS [Nutritional Risk Screening] or PG-SGA [Scored Patient-Generated Subjective Global Assessment]). If risk of malnutrition is present, adequate nutritional therapy is recommended to stop involuntary weight loss. Patients should engage in exercise to maintain and improve muscle mass, strength and function. They should be offered regular dietetic counselling, and their muscle depletion should be monitored by determining fat-free mass. As cachectic patients in particular are at risk, the presence of cachexia should also be recognized at an early stage. Three consensus-based definitions are widely accepted: Fearon et al. and the EPCRC (European Palliative Care Research Collaborative) propose definitions specifically for cancer cachexia, while Evans et al. put forward a definition for cachexia associated with all types of underlying chronic diseases. However, if there is a cancer cachexia diagnosis, additional pharmacological and psychological treatment should be considered.


2002 ◽  
Vol 30 (11) ◽  
pp. 2438-2442 ◽  
Author(s):  
Dennis C. Gore ◽  
David L. Chinkes ◽  
David W. Hart ◽  
Steven E. Wolf ◽  
David N. Herndon ◽  
...  

Pteridines ◽  
1998 ◽  
Vol 9 (1) ◽  
pp. 29-32
Author(s):  
Hiromi Iwagaki ◽  
Akio Hizuta ◽  
Yasuki Nitta ◽  
Noriaki Tanaka

Summary Plasma 5-hydroxytryptamine (serotonin), tryptophan and neopterin levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-γ) production, but decreased serotonin and tryptophan levels. IFN-γ induces a high level of indoleamine dioxvgenase (IDO), a tryptophan degrading enzyme, which in turn increases metabolism along the tryptophan- nicotinic acid pathway, resulting in decreased synthesis of serotonin. These results suggest that persistent immune activation occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism.


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