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A dietary switch promotes sensory neuron–dependent cancer-associated cachexia.

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Title: A dietary switch promotes sensory neuron–dependent cancer-associated cachexia.
Authors: Cross, Michael (AUTHOR), Kotschi, Stefan (AUTHOR), Wu, Warren (AUTHOR), Luciano-Mateo, Fedra (AUTHOR), Kwon, Young-Yon (AUTHOR), Dantas, Ezequiel (AUTHOR), Niazi, Taha (AUTHOR), Chen, Shijia (AUTHOR), Rashidfarrokhi, Ali (AUTHOR), Pillai, Ray (AUTHOR), Sanford, Jack (AUTHOR), Kim, Jeshua (AUTHOR), Hsiang, Juliya (AUTHOR), Gamallo-Lana, Begona (AUTHOR), Mar, Adam C. (AUTHOR), Hao, Yuan (AUTHOR), Rajalingam, Sahith (AUTHOR), Huang, Annie (AUTHOR), Shan, Jackie (AUTHOR), Issa, Habon A. (AUTHOR)
Source: Science. 7/2/2026, Vol. 393 Issue 6806, p90-97. 8p.
Subjects: Cachexia, Prostaglandins, Lung cancer, Peripheral nervous system, Cell communication, High-fat diet, Sensory neurons
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. Editor's summary: Cancer cachexia is a complex metabolic syndrome marked by reduced appetite, weight loss, and muscle wasting. Cross et al. report that a subset of Lkb1-mutant lung cancers is prone to cachexia (see the Perspective by Gültekin and Vander Heiden). When mice were fed a high-calorie, high-fat diet, reduced appetite and weight loss were observed, which was associated with reduced appetite sensing to the brain. Prostaglandin E2 (PGE2) is a lipid-signaling molecule produced by tumors that increases when animals consume fat. The authors found that PGE2 acts locally in the lung to drive decreased weight and appetite. Blocking either PGE2 production or silencing sensory nerves reduced cachexia, suggesting that the peripheral nervous system may represent a therapeutic target. The observations further suggest that tumors can trigger cachexia through local nerve signaling, as opposed to only circulating factors. —Priscilla N. Kelly [ABSTRACT FROM AUTHOR]
Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: A dietary switch promotes sensory neuron–dependent cancer-associated cachexia.
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  Data: <searchLink fieldCode="AR" term="%22Cross%2C+Michael%22">Cross, Michael</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kotschi%2C+Stefan%22">Kotschi, Stefan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wu%2C+Warren%22">Wu, Warren</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Luciano-Mateo%2C+Fedra%22">Luciano-Mateo, Fedra</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kwon%2C+Young-Yon%22">Kwon, Young-Yon</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dantas%2C+Ezequiel%22">Dantas, Ezequiel</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Niazi%2C+Taha%22">Niazi, Taha</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Shijia%22">Chen, Shijia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rashidfarrokhi%2C+Ali%22">Rashidfarrokhi, Ali</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pillai%2C+Ray%22">Pillai, Ray</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sanford%2C+Jack%22">Sanford, Jack</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kim%2C+Jeshua%22">Kim, Jeshua</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hsiang%2C+Juliya%22">Hsiang, Juliya</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gamallo-Lana%2C+Begona%22">Gamallo-Lana, Begona</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mar%2C+Adam+C%2E%22">Mar, Adam C.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hao%2C+Yuan%22">Hao, Yuan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rajalingam%2C+Sahith%22">Rajalingam, Sahith</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang%2C+Annie%22">Huang, Annie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shan%2C+Jackie%22">Shan, Jackie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Issa%2C+Habon+A%2E%22">Issa, Habon A.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Science%22">Science</searchLink>. 7/2/2026, Vol. 393 Issue 6806, p90-97. 8p.
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  Data: <searchLink fieldCode="DE" term="%22Cachexia%22">Cachexia</searchLink><br /><searchLink fieldCode="DE" term="%22Prostaglandins%22">Prostaglandins</searchLink><br /><searchLink fieldCode="DE" term="%22Lung+cancer%22">Lung cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Peripheral+nervous+system%22">Peripheral nervous system</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+communication%22">Cell communication</searchLink><br /><searchLink fieldCode="DE" term="%22High-fat+diet%22">High-fat diet</searchLink><br /><searchLink fieldCode="DE" term="%22Sensory+neurons%22">Sensory neurons</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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. Editor's summary: Cancer cachexia is a complex metabolic syndrome marked by reduced appetite, weight loss, and muscle wasting. Cross et al. report that a subset of Lkb1-mutant lung cancers is prone to cachexia (see the Perspective by Gültekin and Vander Heiden). When mice were fed a high-calorie, high-fat diet, reduced appetite and weight loss were observed, which was associated with reduced appetite sensing to the brain. Prostaglandin E2 (PGE2) is a lipid-signaling molecule produced by tumors that increases when animals consume fat. The authors found that PGE2 acts locally in the lung to drive decreased weight and appetite. Blocking either PGE2 production or silencing sensory nerves reduced cachexia, suggesting that the peripheral nervous system may represent a therapeutic target. The observations further suggest that tumors can trigger cachexia through local nerve signaling, as opposed to only circulating factors. —Priscilla N. Kelly [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=195069941
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        Value: 10.1126/science.adz4196
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      – Code: eng
        Text: English
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        StartPage: 90
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      – SubjectFull: Cachexia
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      – SubjectFull: Prostaglandins
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      – SubjectFull: Lung cancer
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      – SubjectFull: Peripheral nervous system
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      – SubjectFull: Cell communication
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      – SubjectFull: High-fat diet
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      – SubjectFull: Sensory neurons
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