Cancer Cachexia

Amino acid metabolism is hugely altered in tumours. Cancer cells use amino acids for energy production, which supports cell proliferation. In this sense, their amino acid dependency provides a metabolic vulnerability for treatment. Research has been aimed at starving cancerous cells of amino acids to improve cancer treatment outcomes. However, supplementing amino acids has also shown benefits both in vivo and in vitro. Further research into amino acid supplementation is needed, as deprivation exacerbates cancer cachexia, a risk best avoided in cancer treatment. Supplementing branched-chain amino acids has been proved as beneficial in hepatocellular carcinoma, and an essential amino acid rich diet has demonstrated decreased tumour growth in mice. Understanding more about amino acid metabolism in cancer may provide more efficient, personalised treatments for cancer patients.
This review by Ragni M et al. aimed to discuss amino acid deprivation and supplementation in reducing tumour growth, underscoring the complexity of the metabolic pathways involved.

Colorectal cancer is the second leading cause of cancer death in the world. However, incidence rates and mortality can both be significantly reduced through adhering to healthy lifestyle recommendations. In this study, 82 people were included, where their nutritional profile was evaluated to assess their risk of colorectal cancer. This is because obesity is one of the biggest risk factors for colorectal cancer, and when associated with sarcopenia, there are usually worse health outcomes. This study has therefore highlighted the need for understanding muscle composition in obese individuals when screening for cancer, as this may affect outcomes. Furthermore, this study underscores the necessity to aim for health lifestyles through weight control and physical exercise, to decrease incidence and mortality of diseases such as colorectal cancer.
This review by Santos M et al. aimed to evaluate nutritional profiles for those screening for colorectal cancer, to aid a better understanding of the risk factors behind this cancer.

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.

Weight loss is clearly related to cancer, yet there is very little data concerning when and at what stage weight loss should be considered a sign of a need to diagnose cancer. In this study of 43,302 patients, it was found that there was a linear increase in the chance of being diagnosed with cancer compared to the amount of weight lost. This finding was independent of any co-factors, such as age, sex, original weight or co-morbidities. Therefore, it is clear that the percentage of weight lost must be focused on, rather than a guideline with an arbitrary cut-off point for a cancer diagnosis. It could be possible to trigger an alert for patients who lose certain percentages of weight over specified periods of time.
This review by Nicholson B et al aimed to understand the diagnostic value of weight loss in relationship to cancer.

Cancer is often associated with cachexia, a wasting syndrome which is multifactorial and cannot be resolved with simple nutritional aid. It causes loss of muscle mass and is the cause of death for almost a third of cancer patients. However, cachexia is very complex. This muscle-wasting disorder has many underlying mechanisms, whether cancer-induced or chemotherapy induced. Heighted protein catabolism and reduced anabolism, as well as disrupted energy metabolism, are associated with cachexia, but the mechanisms underlying these changes are not fully known. Inflammation and oxidative stress are believed to be important within the mechanisms.
This review by Huot J et al. aimed to evaluate the mechanisms underlying cancer cachexia, particularly discussing the role of oxidative stress.

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.

For patients with advanced-stage cancer, weight loss and lower body mass index has been associated with shorter rates of survival. On the other hand, obesity has been associated with longer survival. Weight loss or cachexia could therefore be used as a prognostic tool, although it has not yet been studied much in clinical trials. It is predicted to be due to the fact that decreased muscle mass is a predictor of shortened survival, as well as lowered nutrient stores and activity level. However, further research is required into understanding weight loss in relation to cancer survival rates, especially in the context of therapies such as chemotherapy, as it is not fully known how this interacts with body mass.
This review by Oswalt C et al. aimed to explore the relationship between body mass index, weight loss and survival rates in advanced lung cancer.

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.