Cancer Cachexia

Many types of conditions and diseases are associated with wasting syndromes such as cachexia. However, despite its prevalence, there is limited knowledge regarding the diagnosis and treatment of cachexia due to our lack of understanding of the causative molecular mechanisms. Cachexia must be viewed through an immunological context to understand its full consequences on patient prognosis. For example, it is known that cytokines such as tumour necrosis factor, IL-1β, IL-6 and IFNγ are consistently upregulated in cases of cachexia in both immune and non-immune cells. This appears to lead to the changes in transcriptional regulation, inducing catabolic pathways in muscles and adipose tissue. Yet, despite this understanding, targeting such cytokines has not shown successful in clinical settings. Further research has also been done to identify the involvement of immune cells such as macrophages, neutrophils, myeloid-derived suppressor cells and T cells in cachexia. Yet, their full involvement in the condition is not yet understood. Hence, many questions remain about this interplay between cachexia and immune system. It is vital to discover the common and unique properties of cancer cachexia and infection-associated cachexia to develop effective therapeutic strategies for cachexia.
This review by Baazim H et al. aimed to highlight the relationship between the immune system and cachexia, as well as our current lack of knowledge surrounding this syndrome.

The guidelines most commonly used to diagnose cachexia are the European Palliative Care Research Collaborative (EPCRC) guidelines. Here, cachexia is classified according to weight loss. However, for patients in palliative care with advanced cancer, there are often cases of oedema and ascites. This hampers the ability to detect weight loss, affecting the likelihood to be diagnosed with cachexia. Therefore, this study wished to examine the validity of diagnosing cachexia based upon other items. Alongside weight loss, this includes factors such as fatigue, decreasing muscle mass in the mid-upper arm, abnormal levels of white blood cells, reduced food intake and others. This study validated the CSS, Cachexia Staging Score, which demonstrated that patients without cachexia had a higher survival rate, and that the risk of mortality was higher with more severe cachexia. They also validated that cachexia prevalence was not significantly different compared to previous studies. Hence, such a multidimensional assessment helps to evaluate disorders including cachexia.
This review by Ueshima J et al. aimed to validate the Cachexia Staging Score for patients with advanced cancer who are under palliative care.

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.

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.