Cancer therapy and cachexia

Thakir, Tuba Mansoor, Wang, Alice R, Decker-Farrell, Amanda R, Ferrer, Miriam, Guin, Rohini N, Kleeman, Sam, Levett, Llewelyn, Zhao, Xiang, Janowitz, Tobias (August 2025) Cancer therapy and cachexia. Journal of Clinical Investigation, 135 (15). ISSN 1558-8238

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Abstract

A central challenge in cancer therapy is the effective delivery of anticancer treatments while minimizing adverse effects on patient health. The potential dual impact of therapy is clearly illustrated in cancer-associated cachexia, a multifactorial syndrome characterized by involuntary weight loss, systemic inflammation, metabolic dysregulation, and behavioral alterations such as anorexia and apathy. While cachexia research often focuses on tumor-driven mechanisms, the literature indicates that cancer therapies themselves, particularly chemotherapies and targeted treatments, can initiate or exacerbate the biological pathways driving this syndrome. Here, we explore how therapeutic interventions intersect with the pathophysiology of cachexia, focusing on key organ systems including muscle, adipose tissue, liver, heart, and brain. We highlight examples such as therapy-induced upregulation of IL-6 and growth-differentiation factor 15, both contributing to reduced nutrient intake and a negative energy balance via brain-specific mechanisms. At the level of nutrient release and organ atrophy, chemotherapies also converge with cancer progression, for example, activating NF-κB in muscle and PKA/CREB signaling in adipose tissue. By examining how treatment timing and modality align with the natural trajectory of cancer cachexia, we underscore the importance of incorporating physiological endpoints alongside tumor-centric metrics in clinical trials. Such integrative approaches may better capture therapeutic efficacy while preserving patient well-being.

Item Type: Paper
Subjects: diseases & disorders
diseases & disorders > neoplasms
diseases & disorders > nutritional and metabolic diseases
diseases & disorders > nutritional and metabolic diseases > cachexia
CSHL Authors:
Communities: CSHL labs > Janowitz lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 1 August 2025
Date Deposited: 07 Aug 2025 12:13
Last Modified: 07 Aug 2025 12:13
PMCID: PMC12321403
Related URLs:
URI: https://repository.cshl.edu/id/eprint/41925

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