Progressive, multi-organ, and multi-layered nature of cancer cachexia

Sep 21, 2026

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Cancer cachexia is a complex, multifaceted condition that undermines patients’ health, treatment efficacy, and economic well-being. Clinical management is hindered by a current definition largely based on late-stage macrosymptoms such as weight loss and sarcopenia, which provide limited actionable clues. Evidence shows cancer-induced host changes extend beyond expectations, involving liver function and immune disruption, and can be detected before visible distant metastases in early localized cancers. The review proposes expanding the definition to encompass all cancer-driven host physiological alterations, enabling a new research perspective.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

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Introduction

Current clinical definition and limitations

Need to capture earlier disease-stage host disruption

Proposed expanded definition and implications

DOI: 10. 1111/cas.16078 R E V I E W A RT I C L E Progressive, multi-organ, and multi-layered nature of cancer cachexia Yuki Nakamura1,2 | Don Pietro Saldajeno1,3 | Kosuke Kawaguchi2 | Shinpei Kawaoka1,4 1Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto, Japan 2Department of Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan 3 Mathematical Informatics Laboratory, Division of Information Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan 4Department of Integrative Bioanalytics, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan Correspondence Shinpei Kawaoka, Department of Integrative Bioanalytics, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Email: [kawaokashinpei@gmail.com](kawaokashinpei@gmail.com) Funding information JST FOREST, Grant/Award Number: 20351876; JSPS KAKENHI, Grant/Award Number: 20H03451, 19K16770 and 21K15530 Abstract Cancer cachexia is a complex, multifaceted condition that negatively impacts the health, treatment efficacy, and economic status of cancer patients. The management of cancer cachexia is an essential clinical need. Cancer cachexia is currently defined mainly according to the severity of weight loss and sarcopenia (i.e., macrosymptoms) . However, such macrosymptoms may be insufficient to give clinicians clues on how to manage this condition as these symptoms appear at the late stage of cancer. We need to understand earlier events during the progression of cancer cachexia so as not to miss a clinical opportunity to control this complex syndrome. Recent research indicates that cancer-induced changes in the host are much wider than previously recognized, including disruption of liver function and the immune system. Furthermore, such changes are observed before the occurrence of visible distant metastases (i.e., in early, localized cancers) . In light of these findings, we propose to expand the definition of cancer cachexia to include all cancer-induced changes to host physiology, including changes caused by early, localized cancers. This new definition of cancer cachexia can provide a new perspective on this topic, which can stimulate the research and development of novel cancer cachexia therapies. K E Y WO R D S cancer cachexia, immunosuppression, liver, metabolism, multiomics 1 | INTRODUCTION Cancer cachexia is currently viewed as a multifactorial syndrome characterized by unintentional loss of appetite, weight, and skeletal muscle, all of which are outward, macrosymptoms. In detail, patients with more than 5% weight loss over the past 6months, or a body mass index of less than 20kg/m2 and ongoing weight loss of more than 2%, or sarcopenia and ongoing weight loss of more than 2% are diagnosed as cachexia1 (Figure 1). It is also suggested that cancer cachexia cannot be completely reversed by nutritional support.1,2 Patients with cancer cachexia often accompany metabolic disorders, systemic inflammation, and active catabolism, but these are currently not used to define cancer cachexia in clinics. Indeed, we do not have specific molecular markers to define cancer cachexia. Cancer cachexia eventually reduces the quality of life and treatment efficacy and increases medical costs (i.e., financial toxicity) in patients.3–5 Despite the well-known negative impacts of cancer cachexia on patients, assessment and management of cancer cachexia is limited and in need of further development.1,2 The current definition of cancer cachexia neither provides a comprehensive picture of cancer-induced host pathophysiology nor Yuki Nakamura and Don Pietro Saldajeno equally contributed to this work. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is

FAQs

Why is the current definition of cancer cachexia considered insufficient for clinical management?

It mainly relies on late-stage macrosymptoms like weight loss and sarcopenia, so it offers limited guidance on earlier, actionable events during progression.

What host changes associated with cancer cachexia may occur before visible metastases?

Cancer-induced alterations can be observed before distant metastases become visible, including disruptions in liver function and the immune system.

What does the proposed expanded definition of cancer cachexia include?

It includes all cancer-induced changes to host physiology, including effects caused by early, localized cancers, not only weight loss and muscle wasting.

Sep 21, 2026

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