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Management of CC is limited by the absence of biomarkers and knowledge of molecules that drive its phenotype. To identify such molecules, we injected 54 human non\u2013small cell lung cancer (NSCLC) lines into immunodeficient mice, 17 of which produced an unambiguous phenotype of cachexia or non-cachexia. Whole-exome sequencing revealed that 8 of 10 cachexia lines, but none of the non-cachexia lines, possessed mutations in serine\/threonine kinase 11 (\n                    <jats:italic>STK11\/LKB1<\/jats:italic>\n                    ), a regulator of nutrient sensor AMPK. Silencing of\n                    <jats:italic>STK11\/LKB1<\/jats:italic>\n                    in human NSCLC and murine colorectal carcinoma lines conferred a cachexia phenotype after cell transplantation into immunodeficient (human NSCLC) and immunocompetent (murine colorectal carcinoma) models. This host wasting was associated with an alteration in the immune cell repertoire of the tumor microenvironments that led to increases in local mRNA expression and serum levels of CC-associated cytokines. Mutational analysis of circulating tumor DNA from patients with NSCLC identified 89% concordance between\n                    <jats:italic>STK11\/LKB1<\/jats:italic>\n                    mutations and weight loss at cancer diagnosis. The current data provide evidence that tumor\n                    <jats:italic>STK11\/LKB1<\/jats:italic>\n                    loss of function is a driver of CC, simultaneously serving as a genetic biomarker for this wasting syndrome.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.165419","type":"journal-article","created":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T14:01:05Z","timestamp":1682258465000},"source":"Crossref","is-referenced-by-count":24,"title":["Tumor loss-of-function mutations in STK11\/LKB1 induce cachexia"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3740-7915","authenticated-orcid":true,"given":"Puneeth","family":"Iyengar","sequence":"first","affiliation":[{"name":"Center for Human Nutrition,"},{"name":"Department of Radiation Oncology,"},{"name":"Harold C. 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