Exosomes are extracellular vesicles that contain cargo such as proteins, lipids, nucleic acids and more. Their function is to alter cell signalling in the cell it releases its cargo into. For example, exosomes have been seen to alter muscle and adipose tissue metabolism. This has led to the thought that they may be involved in cancer cachexia. Inhibiting tumour derived exosome release therefore may improve survival and cancer cachexia in patients. Specifically, tumour derived exosome micro-RNAs have been associated with muscle wasting and tumour presence. Furthermore, they may package inflammatory cytokines. This could play a causal role in cancer cachexia as increase cytokine circulation is thought to precede the loss of appetite in cachexia, holding a causal role in the disease progression.
This review by Pitzer CR et al. aimed to summarise the potential involvement of tumour derived exosomes in cancer cachexia.
Currently, there are many interventions and treatments for cancer cachexia. Early nutritional intervention and care are essential to ensure that sufficient nutritional requirements are met for the patients. This includes oral nutrition where possible, as well as nutrition and exercise therapy. Furthermore, preventive care to minimise loss of skeletal muscle mass is vital. Pharmacological options are also available. These include many options, such as non-steroidal anti-inflammatory drugs, anti-cytokine therapy and eicosapentaenoic acid. Furthermore, steroids are often used for cachexia. However, they have limited effects are limited, so recently, anamorelin hydrochloride, a ligand with a similar action to that of ghrelin, was developed. It is used to treat weight loss by increasing appetite and has been approved for use in cachexia. Anamorelin hydrochloride holds great promise to function as an effective therapeutic drug for cancer cachexia.
This review by Watanabe H & Oshima T aimed to review the current treatments of cancer cachexia, as well as anamorelin hydrochloride, a new and promising treatment.
In this study, TOV21G cancer cachexia mouse models were used to demonstrate impaired muscle function and performance which is seen in cachexia patients. With growth differentiation factor 15, GDF15, neutralization, the mice were seen to exhibit restored muscle function and performance. GDF15 is a stress-responsive cytokine which is secreted by many cells, including tumour cells and damaged cells. GDF15 functions by activating glial cell line-derived neurotrophic factor, GDNF, receptor GFRAL. This is expressed in the hindbrain and leads to reducing food intake and weight loss. This is relevant to cachexia patients, and patients with chronic diseases such as heart failure, as their GDF15 levels are significantly higher than that of healthy people. In this study, the mice were treated with mAB2, an anti-GDF15 antibody. They demonstrated weight gain in terms of fat mass and lean mass, improved muscle function and physical performance. Hence, it is thought that GDF15-related therapy may be effective for patients with cachexia. However, symptoms of cachexia such as fatigue do not appear to be related to GDF15 levels, so further exploration is necessary.
This review by Kim-Muller JY et al. aimed to explore how GDF15 levels are related to weight loss and highlight how GDF15 neutralization could be an option for treating cachexia.
Pancreatic ductal adenocarcinoma, PDAC, is one of the most fatal types of solid tumours. It is also linked to a high prevalence of cachexia, with around 80% of PDAC patients exhibiting cachexia. There is one hypothesis, the endocrine organ–like tumour hypothesis, which aims to explain the reasons behind cancer cachexia occurring during pancreatic ductal adenocarcinoma. Some of the reasons include metabolites, epigenetic changes, hormonal disturbance and genetic instability may be behind the development of cancer cachexia. Generally, the belief is held that metabolic disruption is the process behind cachexia development, but it is also believed there is not one single factor that triggers it.
This review by Yu Y et al aimed to synthesise an understanding of cancer cachexia development and the response of cachexia to current available treatments.
Cancer cachexia has no simple criteria to distinguish its severity in patients. Diagnostic criteria generally includes observing factors such as weight loss, fatigue, abnormal levels of albumin, reduced food intake and others. However, this study explored the cachexia staging score, a method of diagnosing cancer cachexia severity. This score explores strength, walking, rising from a chair, climbing up stairs and how often the patients fall. This allows clinicians to understand the patient’s muscle function. In this study, the cachexia staging score was testing in patients with advanced cancer who are receiving palliative care, to assess its usefulness in these patients. Here, the cachexia staging score was excellent at predicting life expectancy in the patients with advancing cancer receiving palliative care, and was able to classify patients according to their different stages of cachexia. This review by Ueshima J et al. aimed to assess whether the cachexia staging score could be applied to patients with advanced cancer under palliative care.
Cancer cachexia can be mainly categorised with the occurrence of muscle loss, malnutrition and systemic inflammation. Its prognosis can be assessed through the cachexia index, but the use of this index is limited due to it being a complicated procedure with high testing costs. This study explored using a hand grip strength-based cachexia index, testing it with 14, 682 cancer patients. A low hand grip strength index score was found to be associated with high systemic inflammation, high levels of malnutrition and co-morbidities, implying that this index may be associated with disease progression. Overall, using the hand grip strength index for cachexia reflects the muscular and inflammatory conditions of cachexia in one assessment, rather than using multiple such as serum albumin testing, in a simple, non-invasive measure. Furthermore, there is a potential that hand grip strength can provide information about the prognosis of other malignancies.
This review by Xie H et al. aimed to compare the hand grip strength-based cachexia index to the original cachexia index to understand its benefits.
In this study, 102 Japanese patients with gastrointestinal or non-small cell lung cancer with cancer cachexia were used to test anamorelin. Anamorelin is a selective ghrelin receptor agonist and is taken orally. This drug is generally known to increase appetite and was hypothesised to help with improving cancer cachexia as well as increasing the patients’ low body mass index. It was found that improvements in their body weight were durable for up to 24 weeks, and overall, the patients reported a better appetite and overall well-being. The drug was also generally well tolerated, with around 37% of patients experiencing adverse side effects. Most commonly, these included symptoms such as glycosylated haemoglobin increase, peripheral oedema and constipation.
This review by Naito T et al. aimed to understand the benefits of anamorelin in cancer cachexia patients with improving their low body mass index.
Recent studies have identified energy dysregulation as one of the principle drivers of frailty. Exercise, the most effective tool to combat frailty, is associated with energy metabolism upregulation and reduction of inflammation. It has been hypothesised this therapeutic effect is linked to the production of myokines by skeletal muscle in response to acute and chronic exercise. Evidence has concluded that myokines play a crucial role in upholding energy metabolism and combating inflammation. However, despite this, only a limited number of studies have examined the changes in myokine concentrations with exercise in older adults.
This review aims to summarise evidence supporting an association between energy metabolism and frailty. It also assesses the role of myokines, released during exercise, in combating frailty.
Cancer cachexia is a wasting disorder, where nutritional interventions cannot fully aid in restoring weight in patients. It severely impacts quality of life and survival rates of patients. In this study, a 58-question questionnaire was completed by clinicians to understand the knowledge and practice gaps within the treatment of cancer cachexia. Some issues raised included the lack of a standardised definition of cancer cachexia for diagnosis, with 43% of respondents stating that low levels of attention are given to providing such a diagnosis. Furthermore, it was reported that screening for cachexia was not completed routinely, among other practice gaps.
This review by Baracos VE et al. aimed to highlight the gaps in understanding of cancer cachexia that clinicians face worldwide.
Globally, there are over 1.5 million new cases of gastric and oesophageal cancer annually. These cases (especially advanced cases) are often associated with cancer cachexia, a multifactorial syndrome that leads to progressive wasting which cannot be fully reverse through nutritional interventions. It is also responsible for around 20% of cancer deaths. Yet, the understanding of cancer cachexia is often neglected in treatment. This presents an issue as cytotoxic drug doses are most commonly calculated based on body surface area, not taking into account decreasing mass.
Furthermore, understanding cancer cachexia would allow for the improvement of therapeutic options, which are currently little researched, including exercise- and nutrition-based interventions, as well as targeted treatments such as anti-IL1 α and anti-GDF-15. Even for patients with incurable cancers, the management of cachexia wasting can improve quality of life.
This review by Brown LR et al. aimed to highlight the necessity of understanding the progression of cancer cachexia in association with diseases such as gastric and oesophageal cancer, as well as the possible future research directions associated with aiding in these conditions.
Cancer cachexia is a multifactorial syndrome that leads to progressive wasting which cannot be fully reverse through nutritional interventions. There is currently no clear method for the management of cachexia, but exercise seems to hold promising potential. Exercise may provide anti-inflammatory and anti-oxidative effects, which may prove important in aiding with cachexia due to its correlation with inflammation and oxidative stress. Furthermore, exercise improves muscle strength and function, which can improve quality of life for those with cancer cachexia. However, there is very scarce evidence for this, and even some evidence contradicting the benefit of exercise due to the risk of over-extending the patients.
This review by Murphy BT et al. aimed to shine light on both sides of the complex discussion surrounding the benefits of exercise in aiding with cancer cachexia.