Review

. 2023 Apr 27;186(9):1824-1845.

doi: 10.1016/j.cell.2023.03.028.

Cachexia: A systemic consequence of progressive, unresolved disease

Miriam Ferrer¹, Tracy G Anthony², Janelle S Ayres³, Giulia Biffi⁴, Justin C Brown⁵, Bette J Caan⁶, Elizabeth M Cespedes Feliciano⁶, Anthony P Coll⁷, Richard F Dunne⁸, Marcus D Goncalves⁹, Jonas Grethlein¹⁰, Steven B Heymsfield⁵, Sheng Hui¹¹, Mariam Jamal-Hanjani¹², Jie Min Lam¹³, David Y Lewis¹⁴, David McCandlish¹⁵, Karen M Mustian⁸, Stephen O'Rahilly⁷, Norbert Perrimon¹⁶, Eileen P White¹⁷, Tobias Janowitz¹⁸

Affiliations

¹ 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.
² Department of Nutritional Sciences, Rutgers School of Environmental and Biological Sciences, The State University of New Jersey, New Brunswick, NJ 08901, USA.
³ Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
⁴ University of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
⁵ Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
⁶ Kaiser Permanente Northern California Division of Research, Oakland, CA 94612, USA.
⁷ Wellcome Trust-MRC Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK.
⁸ University of Rochester Medical Center, University of Rochester, Rochester, NY 14642, USA.
⁹ Division of Endocrinology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
¹⁰ Ruprecht Karl University of Heidelberg, Heidelberg 69117, Germany.
¹¹ Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
¹² 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.
¹³ Cancer Research UK Lung Cancer Centre of Excellence and Cancer Metastasis Laboratory, University College London Cancer Institute, London WC1E 6DD, UK.
¹⁴ The Beatson Institute for Cancer Research, Cancer Research UK, Glasgow G61 1BD, UK.
¹⁵ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
¹⁶ Department of Genetics, Blavatnik Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
¹⁷ 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.
¹⁸ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Northwell Health Cancer Institute, Northwell Health, New Hyde Park, NY 11042, USA. Electronic address: janowitz@cshl.edu.

PMID: 37116469
PMCID: PMC11059056
DOI: 10.1016/j.cell.2023.03.028

Review

Cachexia: A systemic consequence of progressive, unresolved disease

Miriam Ferrer et al. Cell. 2023.

. 2023 Apr 27;186(9):1824-1845.

doi: 10.1016/j.cell.2023.03.028.

Authors

Affiliations

¹ 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.
² Department of Nutritional Sciences, Rutgers School of Environmental and Biological Sciences, The State University of New Jersey, New Brunswick, NJ 08901, USA.
³ Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
⁴ University of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
⁵ Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
⁶ Kaiser Permanente Northern California Division of Research, Oakland, CA 94612, USA.
⁷ Wellcome Trust-MRC Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK.
⁸ University of Rochester Medical Center, University of Rochester, Rochester, NY 14642, USA.
⁹ Division of Endocrinology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
¹⁰ Ruprecht Karl University of Heidelberg, Heidelberg 69117, Germany.
¹¹ Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
¹² 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.
¹³ Cancer Research UK Lung Cancer Centre of Excellence and Cancer Metastasis Laboratory, University College London Cancer Institute, London WC1E 6DD, UK.
¹⁴ The Beatson Institute for Cancer Research, Cancer Research UK, Glasgow G61 1BD, UK.
¹⁵ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
¹⁶ Department of Genetics, Blavatnik Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
¹⁷ 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.
¹⁸ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Northwell Health Cancer Institute, Northwell Health, New Hyde Park, NY 11042, USA. Electronic address: janowitz@cshl.edu.

PMID: 37116469
PMCID: PMC11059056
DOI: 10.1016/j.cell.2023.03.028

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.

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Conflict of interest statement

Declaration of interests S.O. receives remuneration for scientific advisory services provided to Pfizer, AstraZeneca, Courage Therapeutics, and Third Rock Ventures. M.J.-H. has consulted for, and is a member of, the Achilles Therapeutics Scientific Advisory Board and Steering Committee, has received speaker honoraria from Pfizer, Astex Pharmaceuticals, Oslo Cancer Cluster, and is co-inventor on a European patent application relating to methods to detect lung cancer (PCT/US2017/028013). All authors, other than J.G. and D.M., are members of the CANCAN Grand Challenge Team funded by Cancer Research UK and the National Cancer Institute. The funders had no role in writing or reviewing the manuscript.

Figures

**Figure 1.. Interconnected causes and consequences of disease- or cancer-associated cachexia at organ level.**
Examples of host cell contributors to and organ level consequences of cachexia inducing inflammatory and non-inflammatory processes are illustrated.

**Figure 2.. Specific molecular mediators of organ modulation in cancer progression and cachexia.**
(A) Effect organ matrix for cachexia mediators. (B) Venn diagram of tumor- or host-derived cachexia mediators.

**Figure 3.**
Longitudinal progression of biological phenomena and clinical observations from early cancer to advanced cachexia.

**Figure 4.. Key examples of established pre-clinical model systems for systemic inflammation predisposing or leading to cachexia.**
(A) Venn diagram of physiological cachexia defining aspects of different cancer and non-cancer model systems. (B) Summary categorization of model systems. Note: The assignment of model systems is based on assessment of consensus from the current literature. It is likely that future characterization of model systems will lead to refined allocations.

**Figure 5.. Potential and established contributory areas for the advancement of cachexia research and care.**
Selected aspects relating to the full translational research enterprise from pre-clinical mechanistic work to clinical team building and trial design are listed.

See this image and copyright information in PMC

References

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Cachexia: A systemic consequence of progressive, unresolved disease

Affiliations

Cachexia: A systemic consequence of progressive, unresolved disease

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources