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Beyond cell\u2010intrinsic changes, cancer unfolds as a systemic disease driven by an intricate dialogue between malignant cells and the host's organs and tissues. Modelling this multilayered phenomenon is challenging, as it requires recapitulating coordinated interactions within and across multiple organs, inside an organism that is contended with maintaining normal physiology. In recent years,\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    has emerged as a powerful model for revealing fundamental mechanisms by which the tumour and host mutually interact. In this review, we highlight recent findings that unravel the intricacies of tumour\u2013host biology using\n                    <jats:italic>Drosophila<\/jats:italic>\n                    . At the microenvironment level, we synthesise mechanistic findings on how tumour growth is modulated through interactions with neighbouring tumour subclones, nonmutated wild\u2010type cells and the immune system. At the macroenvironment level, work in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    has provided mechanistic insights into how tumourigenesis causes systemic host health degeneration and accelerates death, collectively termed paraneoplastic effects. Tumours can remotely induce systemic metabolic rewiring and cachectic tissue wasting to promote progression, while simultaneously compromising the function of several tissues, such as the renal system, blood\u2013brain barrier, the gut and blood haemostasis. Additionally, we discuss how the microbiota and sexual dimorphism have been shown to affect the tumour\u2013host interplay. With this review, we synthesise recent advances in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    tumour\u2013host biology and illustrate how this model illuminates cancer's systemic nature.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70207","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T09:57:06Z","timestamp":1768643826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tumour\u2013host interactions in\n                    <i>Drosophila<\/i>\n                    : mechanisms in the tumour micro\u2010 and macroenvironment"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8956-0925","authenticated-orcid":false,"given":"Jos\u00e9","family":"Teles\u2010Reis","sequence":"first","affiliation":[{"name":"Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine University of Oslo  Norway"},{"name":"Department of Molecular Cell Biology, Institute for Cancer Research Oslo University Hospital  Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9150-2676","authenticated-orcid":false,"given":"Tor Erik","family":"Rusten","sequence":"additional","affiliation":[{"name":"Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine University of Oslo  Norway"},{"name":"Department of Molecular Cell Biology, Institute for Cancer Research Oslo University Hospital  Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.016"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2010.0099"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103676"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","DOI":"10.12659\/MSM.947393","article-title":"Review of paraneoplastic syndromes in children with malignancy","volume":"31","author":"Mitur\u2010Lesiuk M","year":"2025","journal-title":"Med Sci Monit"},{"key":"e_1_2_13_6_1","doi-asserted-by":"crossref","DOI":"10.1148\/rg.220085","article-title":"Paraneoplastic syndromes from head to toe: pathophysiology, imaging features, and workup","volume":"43","author":"Badawy M","year":"2023","journal-title":"Radiographics"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00752-w"},{"key":"e_1_2_13_8_1","doi-asserted-by":"crossref","DOI":"10.1177\/10732748241292784","article-title":"Impact of cachexia on chemotherapy efficacy and survival in pancreatic cancer: a systematic review and meta\u2010analysis","volume":"31","author":"Khalil MA","year":"2024","journal-title":"Cancer Control"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advnut.2024.100282"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0488-6"},{"key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fphys.2023.1182610","article-title":"The opportunities and challenges of using Drosophila to model human cardiac diseases","volume":"14","author":"Zhao Y","year":"2023","journal-title":"Front Physiol"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.300167"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07583-x"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-121415-122024"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2021.710652","article-title":"The glucagon\u2010like adipokinetic hormone in Drosophila melanogaster\u2014biosynthesis and secretion","volume":"12","author":"Hughson BN","year":"2021","journal-title":"Front Physiol"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.158865"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301583"},{"key":"e_1_2_13_18_1","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-020-0889-1","article-title":"Trehalose metabolism confers developmental robustness and stability in Drosophila by regulating glucose homeostasis","volume":"3","author":"Matsushita R","year":"2020","journal-title":"Commun Biol"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdev.2021.203760"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.300224"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.119.302289"},{"key":"e_1_2_13_22_1","unstructured":"TheDrosophilaimmunity handbook\u2014Hannah Westlake Mark A. 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