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We demonstrate that among the most common cancer mutations, loss of liver kinase B1 (\n                    <jats:italic toggle=\"yes\">Lkb1<\/jats:italic>\n                    ) 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\n                    <jats:sub>2<\/jats:sub>\n                    ), rather than circulating factors, promotes sickness and that genetic, dietary, and pharmacological inhibition of tumor-derived PGE\n                    <jats:sub>2<\/jats:sub>\n                    suppresses sickness and cachexia. Notably, we demonstrate that lung sensory neuron abrogation prevents PGE\n                    <jats:sub>2<\/jats:sub>\n                    -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.\n                  <\/jats:p>","DOI":"10.1126\/science.adz4196","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:04:19Z","timestamp":1783015459000},"page":"90-97","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["A dietary switch promotes sensory neuron\u2013dependent cancer-associated cachexia"],"prefix":"10.1126","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-9167","authenticated-orcid":true,"given":"Michael","family":"Cross","sequence":"first","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA."},{"name":"Vilcek Institute of Graduate Biomedical Sciences, New York University Grossman School of Medicine, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9857-6291","authenticated-orcid":true,"given":"Stefan","family":"Kotschi","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA."},{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8706-469X","authenticated-orcid":true,"given":"Warren","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA."},{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedra","family":"Luciano-Mateo","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA."},{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-5726","authenticated-orcid":true,"given":"Young-Yon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. 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