{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:59:26Z","timestamp":1790189966625,"version":"4.1.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"868","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NCI R01CA300788"],"award-info":[{"award-number":["NCI R01CA300788"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017458","name":"Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017458","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pershing Square Caner Research Alliance","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,9,23]]},"abstract":"<jats:p>\n                    Leptomeningeal metastasis (LM) is a fatal neurological complication of cancer. Proton craniospinal irradiation (pCSI) has emerged as a promising life-prolonging intervention for patients with LM, but response to this treatment varies. Here, we aimed to characterize the molecular basis of pCSI resistance and response. Proteomic analysis of cerebrospinal fluid (CSF) collected from patients with LM at baseline (before pCSI), and at multiple time points posttreatment, identified the chemokine C-X-C-motif ligand 1, CXCL1, associated with LM growth. Higher CXCL1 levels in the CSF before pCSI correlated with worse response to this treatment. To define the role of CXCL1 in LM, we established syngeneic mouse models of LM-CSI. We found that both metastatic cancer and host cells generate CXCL1. Genetic interruption of\n                    <jats:italic toggle=\"yes\">Cxcl1<\/jats:italic>\n                    expression in metastatic cancer, but not host cells, impaired cancer cell growth within the leptomeninges. Moreover, we found that Cxcr2, the primary receptor for Cxcl1, was widely expressed within the LM microenvironment. A subset of LM cancer cells expressed Cxcr2, and this population was enriched over time in the leptomeninges. Transcriptomic profiling of this rare population revealed enrichment in pathways associated with cell cycle progression. In patients, we found that higher expression of CXCR2 before pCSI correlated with worse overall survival. Last, in preclinical models, interruption of Cxcl1-Cxcr2 signaling with intrathecally delivered Cxcr2 antagonist hampered LM growth and sensitized cancer cells to CSI. Our results demonstrate that the Cxcl1-Cxcr2 signaling axis mediates LM growth and identifies a potential actionable intervention to improve response to pCSI and halt LM progression.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aeh7968","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:00:29Z","timestamp":1790186429000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["CXCL1-CXCR2 signaling mediates cancer cell growth and response to radiation therapy in leptomeningeal metastasis"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5255-2136","authenticated-orcid":true,"given":"Ahmed M.","family":"Osman","sequence":"first","affiliation":[{"name":"Human Oncology &amp; Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Y.","family":"He","sequence":"additional","affiliation":[{"name":"Human Oncology &amp; Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA."},{"name":"Neuroscience Program, Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY 10065, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-2896","authenticated-orcid":true,"given":"Jan","family":"Remsik","sequence":"additional","affiliation":[{"name":"Human Oncology &amp; Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA."},{"name":"Laboratory for Immunology of Metastatic Ecosystems, Center for Cancer Biology, VIB, 3000 Leuven, Belgium."},{"name":"Department of Oncology, KU Leuven, 3000 Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5628-5442","authenticated-orcid":true,"given":"Jenna","family":"Snyder","sequence":"additional","affiliation":[{"name":"Human Oncology &amp; Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA."},{"name":"Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9556-2692","authenticated-orcid":true,"given":"Seogho","family":"Son","sequence":"additional","affiliation":[{"name":"Human Oncology &amp; 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Remsik, Y. Chi, X. Tong, U. Sener, C. Derderian, A. Park, F. Saadeh, T. Bale, A. Boire, Leptomeningeal metastatic cells adopt two phenotypic states. 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J.","year":"2023","unstructured":"A. J. Dunbar, D. Kim, M. Lu, M. Farina, R. L. Bowman, J. L. Yang, Y. Park, A. Karzai, W. Xiao, Z. Zaroogian, K. O\u2019Connor, S. Mowla, F. Gobbo, P. Verachi, F. Martelli, G. Sarli, L. Xia, N. Elmansy, M. Kleppe, Z. Chen, Y. Xiao, E. McGovern, J. Snyder, A. Krishnan, C. Hill, K. Cordner, A. Zouak, M. E. Salama, J. Yohai, E. Tucker, J. Chen, J. Zhou, T. McConnell, A. R. Migliaccio, R. Koche, R. Rampal, R. Fan, R. L. Levine, R. Hoffman, CXCL8\/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis. Blood 141, 2508\u20132519 (2023).","journal-title":"Blood"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521491113"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.10.010"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00297-8"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noae103"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdab108"},{"key":"e_1_3_2_34_2","first-page":"817","article-title":"MR imaging of leptomeningeal metastases: Comparison of three sequences","volume":"23","author":"Singh S. K.","year":"2002","unstructured":"S. K. Singh, N. E. Leeds, L. E. Ginsberg, MR imaging of leptomeningeal metastases: Comparison of three sequences. AJNR Am. J. Neuroradiol. 23, 817\u2013821 (2002).","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"e_1_3_2_35_2","first-page":"e4416","article-title":"Diagnostic reliability of leptomeningeal disease using magnetic resonance imaging","volume":"11","author":"Harris P.","year":"2019","unstructured":"P. Harris, A. Diouf, F. Guilbert, F. Ameur, L. Letourneau-Guillon, C. M\u00e9nard, L. Masucci, M. B\u00e9lair, D. Roberge, Diagnostic reliability of leptomeningeal disease using magnetic resonance imaging. Cureus 11, e4416 (2019).","journal-title":"Cureus"},{"key":"e_1_3_2_36_2","first-page":"vdab181","article-title":"Quantitative cerebrospinal fluid circulating tumor cells are a potential biomarker of response for proton craniospinal irradiation for leptomeningeal metastasis","volume":"3","author":"Wijetunga N. A.","year":"2021","unstructured":"N. A. Wijetunga, A. Boire, R. J. Young, Y. Yamada, S. Wolden, H. Yu, M. Kris, A. Seidman, A. Betof-Warner, M. Diaz, A. Reiner, R. Malani, E. Pentsova, J. T. Yang, Quantitative cerebrospinal fluid circulating tumor cells are a potential biomarker of response for proton craniospinal irradiation for leptomeningeal metastasis. Neurooncol. Adv. 3, vdab181 (2021).","journal-title":"Neurooncol. 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