Journal Article Review Epublish
PubMed: 40759570 DOI: 10.1172/JCI191934
Cancer therapy and cachexia.
J Clin Invest 135(15)
Authors: Tuba Mansoor Thakir, Alice R Wang, Amanda R Decker-Farrell, Miriam Ferrer, Rohini N Guin, Sam Kleeman, Llewelyn Levett, Xiang Zhao, Tobias Janowitz
Affiliations
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA. Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, USA.
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
- Medical Scientist Training Program, Stony Brook University School of Medicine, Stony Brook, New York, USA.
- Stony Brook University, Graduate Program in Genetics, Stony Brook, New York, USA.
- Northwell Health, New Hyde Park, New York, USA.
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.
MeSH
Nutrients, Muscles, Brain, Neoplasms, Drug Therapy, Liver, Food, Therapeutics, Tissues, Cachexia, Adipose Tissue, Chemotherapy, Cancer-Associated Cachexia