Related Experiment Video
Updated: Jul 4, 2026
08:55
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
A dietary switch promotes sensory neuron-dependent cancer-associated cachexia
Michael Cross1,2, Stefan Kotschi1,3, Warren Wu1,3
1Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA.
Science (New York, N.Y.)
|July 2, 2026
Summary
Loss of liver kinase B1 (Lkb1) promotes lung cancer cachexia. Tumor-derived prostaglandin E2 (PGE2) signals to sensory neurons, driving sickness and cachexia, not circulating factors.
Area of Science:
- Oncology
- Neuroscience
- Molecular Biology
Background:
- Cancer-associated cachexia significantly impacts patient quality of life, affecting up to 50% of lung cancer patients.
- Sickness behaviors are a prominent feature of cachexia, complicating patient management and treatment.
- The liver kinase B1 (Lkb1) gene is frequently mutated in common cancers, but its role in cachexia is not well understood.
Purpose of the Study:
- To investigate the role of Lkb1 loss in promoting lung cancer cachexia.
- To identify the specific mechanisms driving cachexia-associated sickness behaviors.
- To explore therapeutic strategies targeting cachexia development.
Main Methods:
- Utilized preclinical models of lung cancer with Lkb1 loss.
- Administered obesogenic high-fat diets to assess impact on cachexia.
- Measured local prostaglandin E2 (PGE2) production and circulating factors.
- Investigated genetic, dietary, and pharmacological inhibition of tumor-derived PGE2.
- Examined the role of lung sensory neurons in cachexia development.
Main Results:
- Loss of Lkb1 promotes cachexia in preclinical lung cancer models.
- Tumor-derived prostaglandin E2 (PGE2), not circulating factors, drives cachexia-associated sickness.
- Inhibition of tumor PGE2 suppressed sickness and cachexia.
- Abrogation of lung sensory neurons prevented PGE2-dependent cachexia.
Conclusions:
- Localized tumor-derived signals, specifically PGE2 acting on sensory neurons, are key drivers of cancer cachexia.
- This study highlights a novel role for the peripheral nervous system in mediating cancer cachexia.
- Targeting tumor-derived PGE2 and its interaction with sensory neurons presents a potential therapeutic avenue for cachexia.
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