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Here, we establish the Atlas of\n                    <jats:italic>Ras<\/jats:italic>\n                    -driven Tumors in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    (ART-D), a systematic, cross-species platform that dissects the molecular and phenotypic trajectories of tumorigenesis across ten genetically defined\n                    <jats:italic>Ras<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V12<\/jats:italic>\n                    <\/jats:sup>\n                    -driven models. By integrating longitudinal phenotypic profiling, we define three conserved stages of tumor development\u2014initiation, promotion, and progression\u2014distinguished by distinct shifts in tumor burden and tumor-induced cachexia. Transcriptomic analysis reveals stage-specific signaling rewiring: early tumorigenesis is characterized by co-activation of JAK\/STAT, NF-\u03baB\/Toll, and MAPK pathways, whereas malignant progression is driven by Notch hyperactivation and Hippo pathway inactivation. Through integrative multi-omics and machine learning, we uncover an evolutionarily conserved pathogenic network coordinating JNK, NF-\u03baB\/Toll, Notch, and Hippo signaling, which we functionally validate across species. ART-D serves as a transformative resource bridging\n                    <jats:italic>Drosophila<\/jats:italic>\n                    genetics and human cancer biology, offering a robust framework for decoding conserved oncogenic principles and identifying of stage-specific vulnerabilities in\n                    <jats:italic>RAS<\/jats:italic>\n                    -driven cancers.\n                  <\/jats:p>","DOI":"10.1038\/s44320-026-00215-8","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:37:29Z","timestamp":1778769449000},"page":"1214-1251","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross-species insights from ART-D to uncover evolutionarily conserved oncogenic mechanisms"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-2945","authenticated-orcid":false,"given":"Yifan","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9195-0364","authenticated-orcid":false,"given":"Yixin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-3463","authenticated-orcid":false,"given":"Wenyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7405-0585","authenticated-orcid":false,"given":"Xianping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-3947","authenticated-orcid":false,"given":"Xianjue","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"215_CR1","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/s43018-023-00575-2","volume":"4","author":"Y Adachi","year":"2023","unstructured":"Adachi Y, Kimura R, Hirade K, Yanase S, Nishioka Y, Kasuga N, Yamaguchi R, Ebi H (2023) Scribble mis-localization induces adaptive resistance to KRAS G12C inhibitors through feedback activation of MAPK signaling mediated by YAP-induced MRAS. 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