A dietary switch promotes sensory neuron–dependent cancer-associated cachexia
- Michael Cross
- Stefan Kotschi
- Warren Wu
- Fedra Luciano-Mateo
- Young-Yon Kwon
- Ezequiel Dantas
- Taha Niazi
- Shijia Chen
- Ali Rashidfarrokhi
- Ray Pillai
- Jack Sanford
- Jeshua Kim
- Juliya Hsiang
- Begoña Gamallo-Lana
- Adam C. Mar
- Yuan Hao
- Sahith Rajalingam
- Annie Huang
- Jackie Shan
- Habon A. Issa
- María Gómez
- Alice R. Wang
- Xiang Zhao
- Tobias Janowitz
- Eileen White
- Yin Liu
- Kwok-kin Wong
- Leopoldo N. Segal
- Sheng Hui
- Marcus D. Goncalves
- Robert C. Froemke
- Thales Papagiannakopoulos
2026-07-02
Sickness behaviors are common in cancer-associated cachexia and affect up to half of lung cancer patients. We demonstrate that among the most common cancer mutations, loss of liver kinase B1 ( Lkb1 ) promotes the development of cachexia in preclinical models of lung cancer. In an effort to improve caloric intake with an obesogenic high-fat diet, we paradoxically observed worsened cachexia-associated sickness. We found that local production of prostaglandin E2 (PGE 2 ), rather than circulating factors, promotes sickness and that genetic, dietary, and pharmacological inhibition of tumor-derived PGE 2 suppresses sickness and cachexia. Notably, we demonstrate that lung sensory neuron abrogation prevents PGE 2 -dependent cachexia. Our study establishes localized tumor-derived signals to sensory neurons, rather than circulating factors, as drivers of cachexia and highlights a previously unknown role of the peripheral nervous system in cancer cachexia.