该研究团队证明，在最常见的癌症突变中，肝激酶B1 （Lkb1）的缺失促进了肺癌临床前模型中恶病质的发展。在努力通过致肥性高脂肪饮食改善热量摄入的过程中，研究组矛盾地观察到恶病质相关疾病的恶化。课题组发现前列腺素E2 （PGE2）的局部产生，而不是循环因子，促进疾病，遗传、饮食和药物抑制肿瘤来源的PGE2抑制疾病和恶病质。
值得注意的是，该课题组人员证明了肺感觉神经元的消除可以防止PGE2依赖性恶病质。他们的研究确定了局部肿瘤来源的信号传递给感觉神经元，而不是循环因子，作为恶病质的驱动因素，并强调了周围神经系统在癌症恶病质中以前未知的作用。
研究人员表示，疾病行为在癌症相关的恶病质中很常见，影响了多达一半的肺癌患者。
附：英文原文
Title: A dietary switch promotes sensory neuron–dependent cancer-associated cachexia
Author: 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, Begona Gamallo-Lana, Adam C. Mar, Yuan Hao, Sahith Rajalingam, Annie Huang, Jackie Shan, Habon A. Issa, Maria Gomez, 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
Issue&Volume: 2026-07-02
Abstract: 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 (PGE2), rather than circulating factors, promotes sickness and that genetic, dietary, and pharmacological inhibition of tumor-derived PGE2 suppresses sickness and cachexia. Notably, we demonstrate that lung sensory neuron abrogation prevents PGE2-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.
DOI: adz4196
Source: https://www.science.org/doi/10.1126/science.adz4196