Cancer cachexia: biomarkers and the influence of age

BackgroundTaste disorders are common in patients with cancer undergoing systemic therapy, persist during treatment and are associated with reduced food intake, increasing the risk of malnutrition. Cachectic syndrome, which is common in these patients and characterized by marked weight loss, anorexia, asthenia and anemia, is linked to the presence and growth of the tumor and leads to systemic inflammation.Synsepalum dulcificumis a plant whose berries contain miraculin, a glycoprotein that transforms sour tastes into sweet ones and could serve to ameliorate taste disorders in patients with cancer.ObjectiveTo evaluate the effect of the regular intake of Dried Miracle Berries (DMB), a novel food containing miraculin, on several biomarkers of inflammation and cachexia in malnourished patients with cancer and taste disorders receiving systemic antineoplastic therapy.Materials and methodsTriple-blind, randomized, placebo-controlled clinical trial. Thirty-one patients with cancer of various etiologies receiving chemotherapy were enrolled in a pilot study and divided into three groups. The first group received a tablet containing 150 mg of DMB (standard dose); the high-dose group received a tablet of 300 mg of DMB, and the third group received a tablet with 300 mg of the placebo for three months before each main meal. Plasma levels of several molecules associated with inflammation and cancer cachexia were measured using the X-MAP Luminex multiplexing platform.ResultsThe three groups showed a decrease in the plasma levels of IL-6, IL-1β, TNF-α, and PIF throughout the intervention, although the percentage change from baseline was greater in patients receiving a standard dose of DMB. In contrast, the CNTF concentration only decreased in the DMB standard-dose group. This group also presented the greatest reduction in the IL-6/ IL-10 ratio, while IL-15 and IL-10 increased in the groups treated with DMB but not in the placebo. Regardless of DMB consumption, sTNFR-II tended to decrease with treatment in patients who responsed well to the antineoplastic treatment. We did not find significant correlations between cytokines and sensory variables or dietary and nutritional status.ConclusionsThe regular consumption of a standard dose of the food supplement DMB containing miraculin along with a systemic antineoplastic treatment can contribute to reducing biomarkers of inflammation and cachexia in malnourished patients with cancer exhibiting taste disorders.

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Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia

Ramos,

Pires,

Gonzalez

et al. 2024

Extracell Vesicles Circ Nucleic Acids

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Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-204-5p, miR-155, miR-425-3p, miR-146b-5p, miR-92a-3p), which can trigger lipolysis and induce the browning of white adipocytes contributing to a cancer cachexia phenotype. On the other hand, adipocyte-derived EVs can reprogram the metabolism of tumor cells by transporting fatty acids and enzymes involved in fatty acid oxidation, resulting in tumor growth and progression. These vesicles also carry leptin and key miRNAs (miR-155-5p, miR-10a-3p, miR-30a-3p, miR-32a/b, miR-21), thereby supporting tumor cell proliferation, metastasis formation, and therapy resistance. Understanding the intricate network underlying EV-mediated communication between tumor cells and adipocytes can provide critical insights into the mechanisms driving cancer cachexia. This review consolidates current knowledge on the crosstalk between tumor cells and adipose tissue mediated by EVs and offers valuable insights for future research. It also addresses controversial topics in the field and possible therapeutic approaches to manage cancer cachexia and ultimately improve patient outcomes and quality of life.

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Cancer cachexia: biomarkers and the influence of age

Cited by 4 publications

References 183 publications

Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG

Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG

The Regular Consumption of a Food Supplement Containing Miraculin Can Contribute to Reducing Biomarkers of Inflammation and Cachexia in Malnourished Patients with Cancer and Taste Disorders: The CLINMIR Pilot Study

Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia

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