ArticleJournal of cachexia, sarcopenia and muscle2016
MAP3K11/GDF15 axis is a critical driver of cancer cachexia.
Article in Journal of cachexia, sarcopenia and muscle, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 175 citations in OpenAlex.
- Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Pooled it
- Targeting Cancer Cachexia: A Mechanistic Evaluation of Anti-GDF-15 Antibody-Based Combination Therapies.Journal of cachexia, sarcopenia and muscle · 2026Trial
- Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.Journal of cachexia, sarcopenia and muscle · 2024Trial
- GDF15 Is Elevated in Conditions of Glucocorticoid Deficiency and Is Modulated by Glucocorticoid Replacement.The Journal of clinical endocrinology and metabolism · 2020Trial
- Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.Cancer discovery · 2026Article
- The Growth and Trends in Cancer-Induced Cachexia Research: A Bibliometric and AI-Guided Visualization Analysis.Cancer reports (Hoboken, N.J.) · 2026Review
- Integrated miRNA-cytokine profiling reveals a molecular signature of cachexia in patients with chronic heart failure.ESC heart failure · 2026Article
- Therapeutic Gfral silencing via antisense oligonucleotides ameliorates cancer-associated cachexia and extends survival in tumor-bearing mice.Cell reports. Medicine · 2026Article
- Functional segregation of body-brain signals in the area postrema.bioRxiv : the preprint server for biology · 2026Article
- Oxaliplatin triggers adipose and muscle wasting through cancer-independent metabolic and CNS pathways in mouse models.Communications biology · 2026Article
- Bilateral versus unilateral injection of Lewis lung carcinoma cells in female mice fed a Western diet: effects on cachexia severity, tumor burden, and tumor ulcerations.BMC research notes · 2026Article
- Embryonic sheep placenta alleviates muscle-fat wasting symptoms and improves gut microbiome dysbiosis in cachexia mice.Biochemistry and biophysics reports · 2026Article
- De novo and scaffold-based design of GDF15 binders for cancer cachexia diagnostics and therapeutics.Experimental & molecular medicine · 2026Article
- Plasma GDF15 increases during hyperinsulinemic hypoglycemia in humans with post-bariatric hypoglycemia and after insulin exposure in mice.Cell reports. Medicine · 2026Observational
- GDF15 in Patients with Autoimmune Primary Adrenal Insufficiency.International journal of molecular sciences · 2026Article
- Review
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Correlation of growth differentiation factor 15 level in esophageal cancer with cachectic indicators and postoperative infectious complication.Esophagus : official journal of the Japan Esophageal Society · 2026Article
- Lower content of cerebrospinal fluid chemokines in patients with cancer cachexia.Acta cirurgica brasileira · 2026Article
- Dependence of energy balance and hypothalamic neuropeptide gene expression on initial tumor load in mice.Frontiers in oncology · 2026Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro-inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome.
methodsGenetically engineered and xenograft tumour models were used to dissect the molecular mechanisms driving cancer cachexia. Cytokine profiling from the plasma of cachectic and non-cachectic cancer patients and mouse models was utilized to correlate circulating cytokine levels with the cachexia phenotype.
resultsUtilizing engineered tumour models we identified MAP3K11/GDF15 pathway activation as a potent inducer of cancer cachexia. Increased expression and high circulating levels of GDF15 acted as a key mediator of this process. In animal models, tumour-produced GDF15 was sufficient to trigger the cachexia phenotype. Elevated GDF15 circulating levels correlated with the onset and progression of cachexia in animal models and in patients with cancer. Inhibition of GDF15 biological activity with a specific antibody reversed body weight loss and restored muscle and fat tissue mass in several cachectic animal models regardless of their complex secreted cytokine profile.
conclusionsThe combination of correlative observations, gain of function, and loss of function experiments validated GDF15 as a key driver of cancer cachexia and as a potential therapeutic target for the treatment and/or prevention of this syndrome.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.