Cachexia: A systemic consequence of progressive, unresolved disease.

Steven B Heymsfield, Tobias Janowitz, Eileen P White, Norbert Perrimon, Stephen O'Rahilly, Karen M Mustian, David McCandlish, David Y Lewis, Jie Min Lam, Mariam Jamal-Hanjani, Sheng Hui, Miriam Ferrer, Jonas Grethlein, Marcus D Goncalves, Richard F Dunne, Anthony P Coll, Elizabeth M Cespedes Feliciano, Bette J Caan, Justin C Brown, Giulia Biffi, Janelle S Ayres, Tracy G Anthony

Journal: Cell 2023;186(9):1824-1845

PMID: 37116469

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Abstract

Cachexia, a systemic wasting condition, is considered a late consequence of diseases, including cancer, organ failure, or infections, and contributes to significant morbidity and mortality. The induction process and mechanistic progression of cachexia are incompletely understood. Refocusing academic efforts away from advanced cachexia to the etiology of cachexia may enable discoveries of new therapeutic approaches. Here, we review drivers, mechanisms, organismal predispositions, evidence for multi-organ interaction, model systems, clinical research, trials, and care provision from early onset to late cachexia. Evidence is emerging that distinct inflammatory, metabolic, and neuro-modulatory drivers can initiate processes that ultimately converge on advanced cachexia.

Address: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; MRC Cancer Unit, University of Cambridge, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK.; Department of Nutritional Sciences, Rutgers School of Environmental and Biological Sciences, The State University of New Jersey, New Brunswick, NJ 08901, USA.; Salk Institute for Biological Studies, La Jolla, CA 92037, USA.; University of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.; Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.; Kaiser Permanente Northern California Division of Research, Oakland, CA 94612, USA.; Wellcome Trust-MRC Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK.; University of Rochester Medical Center, University of Rochester, Rochester, NY 14642, USA.; Division of Endocrinology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.; Ruprecht Karl University of Heidelberg, Heidelberg 69117, Germany.; Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.; Department of Medical Oncology, University College London Hospitals, London WC1E 6DD, UK; Cancer Research UK Lung Cancer Centre of Excellence and Cancer Metastasis Laboratory, University College London Cancer Institute, London WC1E 6DD, UK.; Cancer Research UK Lung Cancer Centre of Excellence and Cancer Metastasis Laboratory, University College London Cancer Institute, London WC1E 6DD, UK.; The Beatson Institute for Cancer Research, Cancer Research UK, Glasgow G61 1BD, UK.; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.; Department of Genetics, Blavatnik Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.; Rutgers Cancer Institute of New Jersey, Department of Molecular Biology and Biochemistry, Rutgers University, The State University of New Jersey, New Brunswick, NJ 08901, USA; Ludwig Princeton Branch, Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA.; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Northwell Health Cancer Institute, Northwell Health, New Hyde Park, NY 11042, USA. Electronic address: [email protected].

DOI: 10.1016/j.cell.2023.03.028

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MeSH Terms: Humans, Cachexia, Muscle, Skeletal, Neoplasms, Infections, Multiple Organ Failure