It affects 80% of advanced stage cancer patients with serious repercussions on the quality of life. It is cachexia that manifests itself with a progressive weakening of the organism, severe organic wasting, weight loss, alteration of psychic abilities and decreased appetite. Unfortunately, it is estimated that at least 20% of all cancer-related deaths are directly caused by cachexia. What can be done to be able to intervene? This is the question on which some Italian researchers are working and which recently led to the publication of two scientific studies that open up new possible prospects for intervention.
Cancer, half of the patients suffer from malnutrition
by Erica Manna
What is cachexia
This condition is often associated with chronic or end-stage disease (particularly cancer) and is characterized by loss of muscle mass with or without loss of fat mass. “It is not a condition exclusive to the advanced stages of the disease; on the contrary, it can be the first symptom of a tumor, for example in tumors of the digestive system “, clarifies Giampiero Porzio, Tuscany Tumor Association – Oncological Home Care and national coordinator of the Continuity of Care Working Group of the Italian Medical Oncology Association (Aiom). The impact of cachexia on the patient and his family is very heavy. “Feeding a loved one is not just feeding calories, but something profound, involving the innermost feelings. In these situations, psychological support for the patient and the family is essential and, even in this case, it must be established as early as possible ”, adds Porzio. For this we need new solutions that can prevent or reduce this disorder.
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The research of the Italian-Belgian team
A team of Italian and Belgian scientists tried to analyze the causes of cachexia in humans and in mouse models. The results, published in Embo Reports, shed light on the mechanisms of wasting in advanced cancer patients. Specifically, the researchers sought to understand whether iron deficiency, already known to be highly prevalent among cancer patients and associated with poor prognosis, is causally linked to cachexia. To do this, severe iron-deficiency anemia typical of cancer patients was induced in mice by a combination of an iron-free diet and phlebotomy (what was once bloodletting).
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Iron supplementation
This actually resulted in muscle atrophy in those mice, supporting the hypothesis that the iron metabolism disturbance is associated with the onset of muscle atrophy in cancer subjects. Not only that: it has been observed that function and muscle mass, but also longer survival in mouse models with colon cancer could be supported by iron supplementation, preventing or reducing cachexia. Intravenous iron injections resulted in healthier, physically active mice that survived well beyond the usual two weeks, as well as a noticeable improvement in grip strength within 24 hours, all of which was maintained until the end of the experiment.
Still early to draw conclusions
But the Italian-Belgian team also looked for ‘evidence’ of their thesis on a small group of cancer patients in whom a moderate improvement in strength was observed a few days after the injection of ferric carboxymaltose, an iron preparation commonly used as a supplement. . “This study – explains Porzio – opens an interesting perspective on the pathogenesis of cachexia in cancer patients. It is a multifactorial disorder involving the complex mechanisms of tumor-host interaction, the side effects of antineoplastic therapies and, most likely, predisposing genetic factors. Therefore, iron supplementation, which is not devoid of side effects, cannot be considered decisive for the treatment of cachexia and must be taken into consideration on a case-by-case basis “.
The molecular target study
Another recent study – supported by the Airc Foundation for Cancer Research and just published in the Journal of Cachexia, Sarcopenia and Muscle – has identified a new molecular target that could help cancer patients with cachexia regain muscle mass and strength. In the study, led by Bert Blaauw, principal investigator at the Venetian Institute of Molecular Medicine (Vimm) and associate professor at the University of Padua, the researchers started by studying a cellular communication pathway, called via Akt-mTOR and formerly known for its role in maintaining the functional balance of the muscle. “It is a pathway that, when active, promotes the growth of muscle fibers,” he explained Bert Blaauw. “At the same time, however, it is known that this pathway is also active in various cancers. For this reason, some of its components are the target of numerous anticancer drugs, which however have as a side effect an increase in muscle wasting. The aim of our research – he continues – is to better understand what happens to the Akt-mTOR pathway in skeletal muscle in a situation of tumor cachexia, both when it is inhibited and when it is reactivated “.
The Akt-m Tor path and the role of physical exercise
In subjects with cancer who show muscle wasting, the researchers observed that the Akt-m TOR pathway is less active than normal. Furthermore, experiments with laboratory animals have shown that reactivation of the pathway through genetic modifications led to an almost complete recovery not only of muscle mass, but also of strength. The researchers’ attention also focused on how to activate the Akt-mTOR pathway. Among these is physical exercise, although it remains to be understood which types of exercises are most effective for this purpose and for how long they must be practiced to obtain a result. “Having this information would allow us to build targeted physical activity plans for patients with cachexia, so that they only have to do what is strictly necessary to have a muscle benefit,” Blaauw points out. Another option could be pharmacological: “There are research groups around the world that are working on techniques to deliver drugs in a precise manner for a given tissue. In the future, these techniques could, for example, allow the activation of Akt-mTOR only in skeletal muscle during tumor cachexia ”concludes Blaauw.
Cachexia in Italy
How many cancer patients in Italy suffer from cachexia? Difficult to give a number because the answer depends on two variables: the location of the tumor and the state of the disease. “Tumors of the gastrointestinal tract – explains Porzio – have a much higher incidence of cachexia than other tumors, for example those of the breast. As regards the state of the disease, in the advanced stages, cachexia is extremely frequent, regardless of the location of the primary tumor “. But how to reduce the incidence of cachexia or, at least, delay its onset? “We have only one possible strategy – replies Porzio – to anticipate the evaluation of the nutritional status and act accordingly, before cachexia becomes irreversible. Furthermore, the monitoring of the nutritional status must be repeated at each visit, in patients under treatment and in those in follow up. In the latter, the outcomes of the therapies can lead to alterations of the nutritional status that persist over time “.
How is it done today
While waiting for some news to arrive from the research, at present there is not much that can be done to counter this syndrome. “Unfortunately, there are no specific therapies, such as, for example, opioid drugs for pain therapy. We have several options: nutritional counseling, drugs capable of stimulating appetite and artificial nutrition, none of which are decisive “, underlines Porzio who specifies:” It is appropriate to underline how cachexia develops by successive steps – pre-cachexia , cachexia and refractory cachexia – and that the chances of success of the therapies are linked to the timing of the intervention. In refractory cachexia any therapy is ineffective, while in pre-cachexia we have a better chance of success. We can say that the best drug we have is time. The patient must be evaluated for his nutritional status at the first visit and any therapies must be started simultaneously with the antineoplastic therapies “.