{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:31:28Z","timestamp":1792794688226,"version":"4.5.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"CCSG"},{"name":"American Lung Association Lung Cancer Discovery","award":["1R01 CA255515-01A1"],"award-info":[{"award-number":["1R01 CA255515-01A1"]}],"id":[{"id":"https:\/\/ror.org\/01p3rh655","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Lung Association Lung Cancer Discovery","award":["P30-CA016056"],"award-info":[{"award-number":["P30-CA016056"]}],"id":[{"id":"https:\/\/ror.org\/01p3rh655","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Preclinical cancer studies ascribe promising anticancer properties to metformin. Yet, clinical findings vary, casting uncertainty on its therapeutic value for non\u2013small cell lung cancer (NSCLC) patients. We hypothesized that metformin could benefit obese and overweight patients with NSCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 2 clinical cohorts and employed complementary mouse models to test our hypothesis. One cohort included NSCLC patients with overweight body mass index (\u226525 kg\/m2, n\u2009=\u2009511) and nonoverweight body mass index (&amp;lt;25 kg\/m2, n\u2009=\u2009232) who underwent lobectomy, evaluating metformin\u2019s impact on clinical outcomes. Another cohort examined metformin\u2019s effect on progression-free survival after immune checkpoint inhibitors in overweight (n\u2009=\u2009284) vs nonoverweight (n\u2009=\u2009184) NSCLC patients. Metformin\u2019s effects on tumor progression, antitumor immunity, and immune checkpoint inhibitor response in obese and normal-weight mice were assessed with lung cancer models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Metformin is associated with increased recurrence-free survival in overweight patients (hazard ratio [HR]\u2009=\u20090.47, 95% confidence interval [CI]\u2009=\u20090.24 to 0.94; P\u2009=\u2009.035) after lobectomy. It also corrected accelerated tumor growth in diet-induced obese mouse models in a lymphocyte-specific manner while reversing several mechanisms of immune suppression potentiated by obesity. Programmed cell death 1 blockade coupled with metformin was more effective at limiting tumor burden in obese mice and correlated with progression-free survival only in overweight patients on immunotherapy (HR\u2009=\u20090.60, 95% CI\u2009=\u20090.39 to 0.93; P\u2009=\u2009.024).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Metformin may improve lung cancer\u2013specific clinical outcomes in obese and overweight lung cancer patients and enhance immunotherapy efficacy in this growing population. This work identifies obesity as a potential predictive biomarker of metformin\u2019s anticancer and immunotherapy-enhancing properties in lung cancer while shedding light on the underlying immunological phenomena.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djae295","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T23:27:14Z","timestamp":1731626834000},"page":"673-684","source":"Crossref","is-referenced-by-count":18,"title":["Obesity-specific improvement of lung cancer outcomes and immunotherapy efficacy with metformin"],"prefix":"10.1093","volume":"117","author":[{"suffix":"Jr.","given":"Randall J","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Immunology, Roswell Park Comprehensive Cancer Center , Buffalo, NY 14263,","place":["United States"]},{"name":"Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center , Buffalo, NY 14263,","place":["United 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Buffalo, NY 14263,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawyer","family":"Bawek","sequence":"additional","affiliation":[{"name":"Department of Medicine, University at Buffalo, State University of New York , Buffalo, NY 14263,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prantesh","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Roswell Park Comprehensive Cancer Center , Buffalo, NY 14263,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer","family":"Rosario","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center , Buffalo, NY 14263,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Barbi","sequence":"additional","affiliation":[{"name":"Department of 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