{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:57:45Z","timestamp":1790402265612,"version":"4.1.0"},"reference-count":130,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Both in situ and allograft models of cancer in juvenile and adult Drosophila melanogaster fruit flies offer a powerful means for unravelling cancer gene networks and cancer\u2013host interactions. They can also be used as tools for cost-effective drug discovery and repurposing. Moreover, in situ modeling of emerging tumors makes it possible to address cancer initiating events\u2014a black box in cancer research, tackle the innate antitumor immune responses to incipient preneoplastic cells and recurrent growing tumors, and decipher the initiation and evolution of inflammation. These studies in Drosophila melanogaster can serve as a blueprint for studies in more complex organisms and help in the design of mechanism-based therapies for the individualized treatment of cancer diseases in humans. This review focuses on new discoveries in Drosophila related to the diverse innate immune responses to cancer-related inflammation and the systemic effects that are so detrimental to the host.<\/jats:p>","DOI":"10.3390\/cells10113211","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T21:32:07Z","timestamp":1637184727000},"page":"3211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Blueprint for Cancer-Related Inflammation and Host Innate Immunity"],"prefix":"10.3390","volume":"10","author":[{"given":"Lucia","family":"Garc\u00eda-L\u00f3pez","sequence":"first","affiliation":[{"name":"Mechanisms of Growth Control and Cancer Lab, Instituto de Neurociencias, CSIC-UMH, Avda. Ram\u00f3n y Cajal s\/n, 03550 Sant Joan d\u2019Alacant, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3337-6883","authenticated-orcid":false,"given":"Isabel","family":"Adrados","sequence":"additional","affiliation":[{"name":"Mechanisms of Growth Control and Cancer Lab, Instituto de Neurociencias, CSIC-UMH, Avda. Ram\u00f3n y Cajal s\/n, 03550 Sant Joan d\u2019Alacant, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0596-4891","authenticated-orcid":false,"given":"Dolors","family":"Ferres-Marco","sequence":"additional","affiliation":[{"name":"Mechanisms of Growth Control and Cancer Lab, Instituto de Neurociencias, CSIC-UMH, Avda. Ram\u00f3n y Cajal s\/n, 03550 Sant Joan d\u2019Alacant, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Mechanisms of Growth Control and Cancer Lab, Instituto de Neurociencias, CSIC-UMH, Avda. Ram\u00f3n y Cajal s\/n, 03550 Sant Joan d\u2019Alacant, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/ijc.31937","article-title":"Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods","volume":"144","author":"Ferlay","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alvarez-Ochoa, E., Froldi, F., and Cheng, L.Y. (2020). Interorgan communication in development and cancer. Wiley Interdiscip. Rev. Dev. Biol., 10.","DOI":"10.1002\/wdev.394"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1016\/j.celrep.2018.02.049","article-title":"PI3K\/Akt Cooperates with Oncogenic Notch by Inducing Nitric Oxide-Dependent Inflammation","volume":"22","author":"Villegas","year":"2018","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1172\/JCI80007","article-title":"Immunity, inflammation, and cancer: An eternal fight between good and evil","volume":"125","author":"Shalapour","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.immuni.2014.06.010","article-title":"Tumor-associated macrophages: From mechanisms to therapy","volume":"41","author":"Noy","year":"2014","journal-title":"Immunity"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1242\/jcs.116392","article-title":"The tumor microenvironment at a glance","volume":"125","author":"Balkwill","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nature02021","article-title":"The immune response of Drosophila","volume":"426","author":"Hoffmann","year":"2003","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1038\/nm.3397","article-title":"Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence","volume":"19","author":"Kottke","year":"2013","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1365-2249.2006.03261.x","article-title":"Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1beta generation","volume":"147","author":"Nielsen","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shaukat, Z., Liu, D., and Gregory, S. (2015). Sterile Inflammation in Drosophila. Mediat. Inflamm., 2015.","DOI":"10.1155\/2015\/369286"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/path.2287","article-title":"TNF-mediated inflammatory disease","volume":"214","author":"Bradley","year":"2008","journal-title":"J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0140-6736(00)04046-0","article-title":"Inflammation and cancer: Back to Virchow?","volume":"357","author":"Balkwill","year":"2001","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Troha, K., and Buchon, N. (2019). Methods for the study of innate immunity in Drosophila melanogaster. Wiley Interdiscip. Rev. Dev. Biol., 8.","DOI":"10.1002\/wdev.344"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.0105-2896.2004.0130.x","article-title":"The immune response of Drosophila melanogaster","volume":"198","author":"Leclerc","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bangi, E. (2013). Drosophila at the intersection of infection, inflammation, and cancer. Front. Cell. Infect. Microbiol., 3.","DOI":"10.3389\/fcimb.2013.00103"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.coi.2019.11.008","article-title":"New insights on Drosophila antimicrobial peptide function in host defense and beyond","volume":"62","author":"Hanson","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, L., Kounatidis, I., and Ligoxygakis, P. (2014). Drosophila as a model to study the role of blood cells in inflammation, innate immunity and cancer. Front. Cell. Infect. Microbiol., 3.","DOI":"10.3389\/fcimb.2013.00113"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1046\/j.1462-5822.2003.00302.x","article-title":"Drosophila blood cells","volume":"5","author":"Meister","year":"2003","journal-title":"Cell. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.4049\/jimmunol.178.8.4711","article-title":"Drosophila Hemopoiesis and Cellular Immunity","volume":"178","author":"Williams","year":"2007","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1534\/genetics.118.300223","article-title":"Drosophila as a Genetic Model for Hematopoiesis","volume":"211","author":"Banerjee","year":"2019","journal-title":"Genetics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1172\/JCI90962","article-title":"The role of the complement system in cancer","volume":"127","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Dudzic, J.P., Kondo, S., Ueda, R., Bergman, C.M., and Lemaitre, B. (2015). Drosophila innate immunity: Regional and functional specialization of prophenoloxidases. BMC Biol., 13.","DOI":"10.1186\/s12915-015-0193-6"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1242\/dmm.000950","article-title":"An innate immune response of blood cells to tumors and tissue damage in Drosophila","volume":"1","author":"Wu","year":"2008","journal-title":"Dis. Models Mech."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tattikota, S.G., Cho, B., Liu, Y., Hu, Y., Barrera, V., Steinbaugh, M.J., Yoon, S.-H., Comjean, A., Li, F., and Dervis, F. (2020). Author response: A single-cell survey of Drosophila blood. eLife, 9.","DOI":"10.7554\/eLife.54818"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1357-2725(97)00123-4","article-title":"Leukotriene B4","volume":"30","author":"Crooks","year":"1998","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jinsphys.2007.09.004","article-title":"Eicosanoids mediate insect hemocyte migration","volume":"54","author":"Merchant","year":"2008","journal-title":"J. Insect Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/0090-6980(86)90195-4","article-title":"Cyclooxygenase and lipoxygenase-like activity in Drosophila melanogaster","volume":"32","author":"Casas","year":"1986","journal-title":"Prostaglandins"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12418","DOI":"10.1073\/pnas.91.26.12418","article-title":"Eicosanoids mediate insect nodulation responses to bacterial infections","volume":"91","author":"Miller","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/bjc.1996.422","article-title":"Inhibition of tumour growth by lipoxygenase inhibitors","volume":"74","author":"Hussey","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1534\/genetics.115.178053","article-title":"Nitric Oxide Synthase Regulates Growth Coordination during Drosophila melanogaster Imaginal Disc Regeneration","volume":"200","author":"Jaszczak","year":"2015","journal-title":"Genetics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nrc1910","article-title":"The role of nitric oxide in tumour progression","volume":"6","author":"Fukumura","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.prostaglandins.2011.08.004","article-title":"Regulation of inflammation in cancer by eicosanoids","volume":"96","author":"Greene","year":"2011","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1254\/jphs.FP0060651","article-title":"Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer","volume":"103","author":"Ihara","year":"2007","journal-title":"J. Pharmacol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Panettieri, S., Paddibhatla, I., Chou, J., Rajwani, R., Moore, R.S., Goncharuk, T., John, G., and Govind, S. (2019). Discovery of aspirin-triggered eico-sanoid-like mediators in a Drosophila metainflammation blood tumor model. J. Cell Sci., 133.","DOI":"10.1242\/jcs.236141"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0960-9822(02)00954-5","article-title":"Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily","volume":"12","author":"Moreno","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1093\/emboj\/cdf306","article-title":"Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway","volume":"21","author":"Igaki","year":"2002","journal-title":"EMBO J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc2628","article-title":"Tumour necrosis factor and cancer","volume":"9","author":"Balkwill","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E7291","DOI":"10.1073\/pnas.1701791114","article-title":"Feedback amplification loop drives malignant growth in epithelial tissues","volume":"114","author":"Muzzopappa","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.smim.2014.05.003","article-title":"The Drosophila TNF ortholog Eiger: Emerging physiological roles and evolution of the TNF system","volume":"26","author":"Igaki","year":"2014","journal-title":"Semin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.devcel.2009.01.002","article-title":"Intrinsic Tumor Suppression and Epithelial Maintenance by Endocytic Activation of Eiger\/TNF Signaling in Drosophila","volume":"16","author":"Igaki","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Froldi, F., Ziosi, M., Garoia, F., Pession, A., Grzeschik, N.A., Bellosta, P., Strand, D., Richardson, H.E., Pession, A., and Grifoni, D. (2010). The lethal giant larvaetumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy. BMC Biol., 8.","DOI":"10.1186\/1741-7007-8-33"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5769","DOI":"10.1093\/emboj\/cdg548","article-title":"Scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic over-growth in Drosophila","volume":"22","author":"Brumby","year":"2003","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1073\/pnas.1113882109","article-title":"Tumor suppression by cell competition through regulation of the Hippo pathway","volume":"109","author":"Chen","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.cub.2006.04.042","article-title":"Loss of Cell Polarity Drives Tumor Growth and Invasion through JNK Activation in Drosophila","volume":"16","author":"Igaki","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.1038\/sj.emboj.7601401","article-title":"JNK- and Fos-regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila","volume":"25","author":"Uhlirova","year":"2006","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2016.12.022","article-title":"Systemic Immunity Is Re-quired for Effective Cancer Immunotherapy","volume":"168","author":"Spitzer","year":"2017","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.celrep.2014.01.039","article-title":"Transformed Epithelia Trigger Non-Tissue-Autonomous Tumor Suppressor Response by Adipocytes via Activation of Toll and Eiger\/TNF Signaling","volume":"6","author":"Parisi","year":"2014","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S1534-5807(03)00244-2","article-title":"Signaling Role of Hemocytes in Drosophila JAK\/STAT-Dependent Response to Septic Injury","volume":"5","author":"Agaisse","year":"2003","journal-title":"Dev. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cell.2012.08.019","article-title":"Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion","volume":"151","author":"Rajan","year":"2012","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nature08702","article-title":"Interaction between RasV12 and scribbled clones induces tumour growth and invasion","volume":"463","author":"Wu","year":"2010","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Bossuyt, W., De Geest, N., Aerts, S., Leenaerts, I., Marynen, P., and Hassan, B.A. (2009). The Atonal Proneural Transcription Factor Links Differentiation and Tumor Formation in Drosophila. PLoS Biol., 7.","DOI":"10.1371\/journal.pbio.1000040"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6222","DOI":"10.1038\/sj.onc.1208757","article-title":"The hScrib\/Dlg apico-basal control complex is differentially targeted by HPV-16 and HPV-18 E6 proteins","volume":"24","author":"Thomas","year":"2005","journal-title":"Oncogene"},{"key":"ref_55","first-page":"593","article-title":"hScrib, a Human Homolog of Drosophila Neoplastic Tumor Suppressor, Is Involved in the Progress of Endometrial Cancer","volume":"18","author":"Ouyang","year":"2009","journal-title":"Oncol. Res. Featur. Preclin. Clin. Cancer Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1053\/j.seminoncol.2014.02.005","article-title":"Tumor Macroenvironment and Metabolism","volume":"41","author":"Huang","year":"2014","journal-title":"Semin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/ijc.1332","article-title":"Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients","volume":"93","author":"Bosaeus","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1038\/bjc.2014.90","article-title":"Cancer and systemic inflammation: Treat the tumour and treat the host","volume":"110","author":"Roxburgh","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nrclinonc.2012.209","article-title":"Understanding the mechanisms and treatment options in cancer cachexia","volume":"10","author":"Fearon","year":"2012","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/s41556-020-00628-z","article-title":"Tumour-derived Dilp8\/INSL3 induces cancer anorexia by regulating feeding neuropeptides via Lgr3\/8 in the brain","volume":"23","author":"Yeom","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1152\/physrev.00016.2008","article-title":"Mechanisms of Cancer Cachexia","volume":"89","author":"Tisdale","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1001\/jama.1980.03310040056033","article-title":"Nutritional care of the cancer patient","volume":"244","author":"DeWys","year":"1980","journal-title":"JAMA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nrc927","article-title":"Cachexia in cancer patients","volume":"2","author":"Tisdale","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1517\/14712598.2010.503773","article-title":"Anti-cytokine strategies for the treatment of cancer-related anorexia and cachexia","volume":"10","author":"Penna","year":"2010","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_67","first-page":"E289","article-title":"Differential gene expression in a murine model of cancer cachexia","volume":"281","author":"Monitto","year":"2001","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/jcsm.12009","article-title":"Improved body weight and performance status and reduced serum PGE2 levels after nutritional intervention with a specific medical food in newly diagnosed patients with esophageal cancer or adenocarcinoma of the gastro-esophageal junction","volume":"6","author":"Faber","year":"2015","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1126\/science.3839597","article-title":"A macrophage factor inhibits adipocyte gene expression: An in vitro model of cachexia","volume":"229","author":"Torti","year":"1985","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0165-2478(85)90165-8","article-title":"Weight loss associated with an endotoxin-induced mediator from peritoneal macrophages: The role of cachectin (tumor necrosis factor)","volume":"11","author":"Cerami","year":"1985","journal-title":"Immunol. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/SPC.0000000000000091","article-title":"Role of interleukin-6 in cachexia: Therapeutic implications","volume":"8","author":"Narsale","year":"2014","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.lfs.2016.11.033","article-title":"TNF-\u03b1 and cancer cachexia: Molecular insights and clinical implications","volume":"170","author":"Patel","year":"2017","journal-title":"Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/jcb.10601","article-title":"Skeletal muscle metabolism in physiology and in cancer disease","volume":"90","author":"Giordano","year":"2003","journal-title":"J. Cell. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Onesti, J.K., and Guttridge, D.C. (2014). Inflammation Based Regulation of Cancer Cachexia. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/168407"},{"key":"ref_75","first-page":"1107","article-title":"Understanding tumor anabolism and patient catabolism in cancer-associated cachexia","volume":"7","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1172\/JCI115767","article-title":"Evidence for the involvement of interleukin 6 in experimental cancer cachexia","volume":"89","author":"Strassmann","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4251\/wjgo.v7.i4.17","article-title":"Cancer cachexia, mechanism and treatment","volume":"7","author":"Aoyagi","year":"2015","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Han, J., Meng, Q., Shen, L., and Wu, G. (2018). Interleukin-6 induces fat loss in cancer cachexia by promoting white adipose tissue lipolysis and browning. Lipids Health Dis., 17.","DOI":"10.1186\/s12944-018-0657-0"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Hodgson, J.A., Parvy, J.-P., Yu, Y., Vidal, M., and Cordero, J.B. (2021). Drosophila Larval Models of Invasive Tumourigenesis for In Vivo Studies on Tumour\/Peripheral Host Tissue Interactions during Cancer Cachexia. Int. J. Mol. Sci., 22.","DOI":"10.1101\/2021.07.01.450696"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1146\/annurev-cellbio-100814-125523","article-title":"Stress Signaling Between Organs in Metazoa","volume":"31","author":"Perrimon","year":"2015","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1126\/science.1216735","article-title":"Imaginal Discs Secrete Insulin-Like Peptide 8 to Mediate Plasticity of Growth and Maturation","volume":"336","author":"Garelli","year":"2012","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1126\/science.1216689","article-title":"Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing","volume":"336","author":"Colombani","year":"2012","journal-title":"Science"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Vallejo, D.M., Juarez-Carre\u00f1o, S., Bolivar, J., Morante, J., and Dominguez, M. (2015). A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3. Science, 350.","DOI":"10.1126\/science.aac6767"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1016\/j.cub.2015.09.020","article-title":"Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability","volume":"25","author":"Colombani","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Garelli, A., Heredia, F., Casimiro, A., Macedo, A., Nunes, C., Garcez, M., Angela, R., Dias, M., Volonte, Y.A., and Uhlmann, T. (2015). Dilp8 requires the neuronal relaxin recep-tor Lgr3 to couple growth to developmental timing. Nat. Commun., 6.","DOI":"10.1038\/ncomms9732"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/nature04376","article-title":"Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb silencing","volume":"439","author":"Vallejo","year":"2006","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Hamaratoglu, F., and Atkins, M. (2020). Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134580"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.devcel.2015.02.012","article-title":"Systemic organ wasting induced by localized expression of the secreted insulin\/IGF antagonist ImpL2","volume":"33","author":"Kwon","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_89","first-page":"23","article-title":"Developmental capacities of benign and malignant neoplasms of Drosophila","volume":"176","author":"Gateff","year":"1974","journal-title":"Dev. Genes Evol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.devcel.2015.03.001","article-title":"Malignant Drosophila Tumors Interrupt Insulin Signaling to Induce Cachexia-like Wasting","volume":"33","author":"Bilder","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Honegger, B., Galic, M., K\u00f6hler, K., Wittwer, F., Brogiolo, W., Hafen, E., and Stocker, H. (2008). Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance. J. Biol., 7.","DOI":"10.1186\/jbiol72"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0304-3835(99)00086-5","article-title":"Insulin resistance was connected with the alterations of substrate utilization in patients with cancer","volume":"141","author":"Yoshikawa","year":"1999","journal-title":"Cancer Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s13539-011-0051-5","article-title":"The role of insulin resistance in the development of muscle wasting during cancer cachexia","volume":"3","author":"Honors","year":"2012","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.devcel.2018.12.003","article-title":"Tumor-Derived Ligands Trigger Tumor Growth and Host Wasting via Differential MEK Activation","volume":"48","author":"Song","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Penna, F., Costamagna, D., Fanzani, A., Bonelli, G., Baccino, F.M., and Costelli, P. (2010). Muscle Wasting and Impaired Myogenesis in Tumor Bearing Mice Are Prevented by ERK Inhibition. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013604"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.ajpath.2012.12.023","article-title":"Autophagic Degradation Contributes to Muscle Wasting in Cancer Cachexia","volume":"182","author":"Penna","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Aversa, Z., Pin, F., Lucia, S., Penna, F., Verzaro, R., Fazi, M., Colasante, G., Tirone, A., Fanelli, F.R., and Ramaccini, C. (2016). Autophagy is induced in the skeletal muscle of cachectic cancer patients. Sci. Rep., 6.","DOI":"10.1038\/srep30340"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Pettersen, K., Andersen, S., Degen, S., Tadini, V., Grosjean, J., Hatakeyama, S., Tesfahun, A.N., Moestue, S.A., Kim, J., and Nonstad, U. (2017). Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02088-2"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Ngabire, D., and Kim, G.-D. (2017). Autophagy and Inflammatory Response in the Tumor Microenvironment. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18092016"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1172\/JCI73941","article-title":"The role for autophagy in cancer","volume":"125","author":"White","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-3-030-23629-8_7","article-title":"Autophagy and Tumorigenesis in Drosophila","volume":"1167","author":"Khezri","year":"2019","journal-title":"Drosoph. Model Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1038\/onc.2017.175","article-title":"Autophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species","volume":"36","author":"Manent","year":"2017","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/cdd.2014.150","article-title":"Oxidative stress and autophagy: The clash between damage and metabolic needs","volume":"22","author":"Filomeni","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature20815","article-title":"Microenvironmental autophagy promotes tumour growth","volume":"541","author":"Katheder","year":"2017","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/(SICI)1098-1128(199905)19:3<223::AID-MED3>3.0.CO;2-N","article-title":"The Role of Cytokines in Cancer Cachexia","volume":"19","author":"Busquets","year":"1999","journal-title":"Med. Res. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Bunker, B.D., Nellimoottil, T.T., Boileau, R.M., Classen, A.K., and Bilder, D. (2015). The Transcriptional Response to Tumorigenic Polarity Loss in Drosophila. eLife, 4.","DOI":"10.7554\/eLife.03189"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1126\/science.1209418","article-title":"Lipases in cachexia","volume":"333","author":"Arner","year":"2011","journal-title":"Science"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1158\/0008-5472.CAN-06-4585","article-title":"Mechanism of Increased Lipolysis in Cancer Cachexia","volume":"67","author":"Agustsson","year":"2007","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1126\/science.1198973","article-title":"Adipose triglyceride lipase contributes to cancer-associated cachexia","volume":"333","author":"Das","year":"2011","journal-title":"Science"},{"key":"ref_110","unstructured":"(2021, October 27). Diet and Cancer|Cancer Research UK. Available online: https:\/\/www.cancerresearchuk.org\/about-cancer\/causes-of-cancer\/diet-and-cancer."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11892-012-0356-6","article-title":"The links between insulin resistance, diabetes, and cancer","volume":"13","author":"Orgel","year":"2013","journal-title":"Curr. Diabetes Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev-pathol-012615-044359","article-title":"Obesity, Inflammation, and Cancer","volume":"11","author":"Deng","year":"2016","journal-title":"Annu. Rev. Pathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1242\/dmm.007948","article-title":"A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila","volume":"4","author":"Musselman","year":"2011","journal-title":"Dis. Models Mech."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.cell.2013.06.030","article-title":"Transformed Drosophila Cells Evade Diet-Mediated Insulin Resistance through Wingless Signaling","volume":"154","author":"Hirabayashi","year":"2013","journal-title":"Cell"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Hirabayashi, S., and Cagan, R.L. (2015). Salt-inducible kinases mediate nutrient-sensing to link dietary sugar and tumorigenesis in Drosophila. eLife, 4.","DOI":"10.7554\/eLife.08501"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Newton, H., Wang, Y.-F., Camplese, L., Mokochinski, J.B., Kramer, H.B., Brown, A.E.X., Fets, L., and Hirabayashi, S. (2020). Systemic muscle wasting and coordinated tumour response drive tumourigenesis. Nat. Commun., 11.","DOI":"10.1038\/s41467-020-18502-9"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.immuni.2014.12.023","article-title":"Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet","volume":"42","author":"Woodcock","year":"2015","journal-title":"Immunity"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature08619","article-title":"Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila","volume":"462","author":"Grandison","year":"2009","journal-title":"Nature"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Nowak, K., Seisenbacher, G., Hafen, E., and Stocker, H. (2013). Nutrient restriction enhances the proliferative potential of cells lacking the tumor suppressor PTEN in mitotic tissues. eLife, 2.","DOI":"10.7554\/eLife.00380"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Nowak, K., Gupta, A., and Stocker, H. (2018). FoxO restricts growth and differentiation of cells with elevated TORC1 activity under nutrient restriction. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007347"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.devcel.2010.05.014","article-title":"Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter","volume":"18","author":"Cordero","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nature14298","article-title":"The Drosophila TNF receptor Grindelwald couples loss of cell polarity and neoplastic growth","volume":"522","author":"Andersen","year":"2015","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.cell.2015.08.016","article-title":"Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression","volume":"162","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.cell.2015.08.012","article-title":"Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses","volume":"162","author":"Ho","year":"2015","journal-title":"Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1111\/jcmm.12794","article-title":"Hypothesis: Solid tumours behave as systemic metabolic dictators","volume":"20","author":"Lee","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_126","first-page":"376","article-title":"Tumor-associated macrophages: Function, phenotype, and link to prognosis in human lung cancer","volume":"4","author":"Quatromoni","year":"2012","journal-title":"Am. J. Transl. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1182\/blood-2006-07-035972","article-title":"Inhibitory effect of tumor cell\u2013derived lactic acid on human T cells","volume":"109","author":"Fischer","year":"2007","journal-title":"Blood"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Martin, A., Sun, E.W.-L., Rogers, G., and Keating, D.J. (2019). The Influence of the Gut Microbiome on Host Metabolism Through the Regulation of Gut Hormone Release. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00428"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Koyle, M.L., Veloz, M., Judd, A.M., Wong, A.C.-N., Newell, P.D., Douglas, A.E., and Chaston, J.M. (2016). Rearing the Fruit Fly Drosophila melanogaster Under Axenic and Gnotobiotic Conditions. JoVE J. Vis. Exp., 113.","DOI":"10.3791\/54219-v"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/bs.ctdb.2016.07.008","article-title":"Modeling Human Cancers in Drosophila","volume":"121","author":"Sonoshita","year":"2017","journal-title":"Curr. Top. Dev. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3211\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:31:48Z","timestamp":1760167908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":130,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cells10113211"],"URL":"https:\/\/doi.org\/10.3390\/cells10113211","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,17]]}}}