Drosophila Model in Cancer: An Introduction

  • Deeptiman Chatterjee
  • Wu-Min DengEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1167)


Cancer is a cumulative manifestation of several complicated disease states that affect multiple organs. Over the last few decades, the fruit fly Drosophila melanogaster, has become a successful model for studying human cancers. The genetic simplicity and vast arsenal of genetic tools available in Drosophila provides a unique opportunity to address questions regarding cancer initiation and progression that would be extremely challenging in other model systems. In this chapter we provide a historical overview of Drosophila as a model organism for cancer research, summarize the multitude of genetic tools available, offer a brief comparison between different model organisms and cell culture platforms used in cancer studies and briefly discuss some of the latest models and concepts in recent Drosophila cancer research.


Cancer Tumorigenesis Drosophila Animal models Genetic tools Cell competition Apoptosis induced proliferation Cachexia Tumor hotspots Drug discovery 



We thank G. Calvin, D. Corcoran, J. Kennedy, E. Lee, J. Poulton, and G. Xie for critical reading of the manuscript. W.-M.D. is supported by Florida Department of Health 8 BC12, National Science Foundation IOS-1052333, and National Institutes of Health R01GM072562 and R01CA224381.


  1. 1.
    Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin [Internet]. 2019 Jan 1 [cited 2019 Feb 28];69(1):7–34. Available from:
  2. 2.
    Hastings KG, Boothroyd DB, Kapphahn K, Hu J, Rehkopf DH, Cullen MR et al (2018) Socioeconomic differences in the epidemiologic transition from heart disease to Cancer as the leading cause of death in the United States, 2003 to 2015. Ann Intern Med 169(12):836. Available from: [Internet, cited 2019 Feb 28]PubMedCrossRefGoogle Scholar
  3. 3.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70. [Internet]. Available from: Scholar
  4. 4.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. [Internet]. Available from: Scholar
  5. 5.
    Polesello C, Roch F, Gobert V, Haenlin M, Waltzer L (2011) Modeling cancers in Drosophila. Prog Mol Biol Transl Sci 100:51–82PubMedCrossRefGoogle Scholar
  6. 6.
    Cheng LY, Parsons LM, Richardson HE (2013) Modelling cancer in drosophila: the next generation. eLS:1–17. [Internet]. Available from:
  7. 7.
    Sonoshita M, Cagan RL (2017) Modeling human cancers in Drosophila. Curr Top Dev Biol 121:287–309. [Internet. Cited 2019 Jan 22]; Available from: Scholar
  8. 8.
    Potter CJ, Turenchalk GS, Xu T (2000) Drosophila in cancer research: an expanding role. Trends Genet 16(1):33–39. [Internet, cited 2019 May 3]. Available from: Scholar
  9. 9.
    Bellen HJ, Tong C, Tsuda H (2010) 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nat Rev Neurosci 11(7):514–522. [Internet. cited 2019 May 3]. Available from: Scholar
  10. 10.
    Kaufman TC (2017) A short history and description of Drosophila melanogaster classical genetics: chromosome aberrations, forward genetic screens, and the nature of mutations. Genetics 206(2):665–689. [Internet. cited 2019 Feb 27]. Available from: Scholar
  11. 11.
    Hales KG, Korey CA, Larracuente AM, Roberts DM (2015) Genetics on the Fly: a primer on the Drosophila model system. Genetics 201(3):815–842. [Internet. cited 2019 May 3]Available from: Scholar
  12. 12.
    Brumby AM, Richardson HE (2005) Using Drosophila melanogaster to map human cancer pathways. Nat Rev Cancer 5(August):626–639PubMedCrossRefGoogle Scholar
  13. 13.
    Bangi E (2013) Drosophila at the intersection of infection, inflammation, and cancer. Front Cell Infect Microbiol [Internet] 3(December):103. Available from: Scholar
  14. 14.
    Giacomotto J, Ségalat L (2010) High-throughput screening and small animal models, where are we? Br J Pharmacol 160(2):204–216PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Bernards A, Hariharan IK (2001) Of flies and men - studying human disease in Drosophila. Curr Opin Genet Dev 11(3):274–278. [Internet. Cited 2019 Apr 28]. Available from: Scholar
  16. 16.
    Reiter LT, Potocki L, Chien S, Gribskov M, Bier E (2001) A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res 11(6):1114–1125. [Internet, cited 2019 Apr 28]. Available from: Scholar
  17. 17.
    Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G et al (2014) A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell 159(1):200–214. [Internet]. [cited 2019 Apr 28]. Available from: Scholar
  18. 18.
    Grifoni D, Froldi F, Pession A (2013) Connecting epithelial polarity, proliferation and cancer in Drosophila: the many faces of lgl loss of function. Int J Dev Biol 57(9–10):677–687PubMedCrossRefGoogle Scholar
  19. 19.
    Amoyel M, Bach EA (2014) Cell competition: how to eliminate your neighbours. Development [Internet] 141(5):988–1000. Available from: Scholar
  20. 20.
    Fogarty CE, Diwanji N, Lindblad JL, Tare M, Amcheslavsky A, Makhijani K et al (2016) Extracellular reactive oxygen species drive apoptosis-induced proliferation via Drosophila macrophages. Curr Biol 26(5):575–584PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Tamori Y, Deng WM (2014) Compensatory cellular hypertrophy: the other strategy for tissue homeostasis. Trends Cell Biol 24(4):230–237. [Internet]. Available from: Scholar
  22. 22.
    Enomoto M, Carmen S, Igaki T (2018) Drosophila as a Cancer model. In: Yamaguchi M (ed) Drosophila models for human diseases. 1070th ed. springer nature Singapore Pte ltd, pp 173–194CrossRefGoogle Scholar
  23. 23.
    Rudrapatna VA, Cagan RL, Das TK (2012) Drosophila cancer models. Dev Dyn 241(October 2011):107–118PubMedCrossRefGoogle Scholar
  24. 24.
    Read RD (2011) Drosophila melanogaster as a model system for human brain cancers. Glia 59(9):1364–1376. [Internet]. [cited 2019 Apr 27]. Available from: Scholar
  25. 25.
    Miles WO, Dyson NJ, Walker J (2011) Modeling tumor invasion and metastasis in Drosophila. Dis Model Mech 4(6):753–761PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Richardson E (2015) H. Drosophila models of cancer. AIMS Genet [Internet] 2(1):97–103. Available from: Scholar
  27. 27.
    Alderson T (1965) Chemically induced delayed germinal mutation in Drosophila. Nature 207(993):164–167. [Internet]. [cited 2019 Feb 27]. Available from: Scholar
  28. 28.
    Muller HJ (1928) The production of mutations by X-rays. Proc Natl Acad Sci U S A 14(9):714–726. [Internet] [cited 2019 May 3]. Available from: Scholar
  29. 29.
    St Johnston D (2002) The art and design of genetic screens: Drosophila melanogaster. Nat Rev Genet 3(3):176–188. [Internet] [cited 2019 Feb 27]. Available from: Scholar
  30. 30.
    Venken KJT, Bellen HJ (2005) Emerging technologies for gene manipulation in drosophila melanogaster. Nat Rev Genet 6:167–178. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  31. 31.
    Venken KJT, Schulze KL, Haelterman NA, Pan H, He Y, Evans-Holm M et al (2011) MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes. Nat Methods 8(9):737–743. [Internet] [cited 2019 May 3]. Available from: Scholar
  32. 32.
    Bellen HJ, Levis RW, He Y, Carlson JW, Evans-Holm M, Bae E et al (2011) The drosophila gene disruption project: progress using transposons with distinctive site specificities. Genetics 188(3):731–743. [Internet] [cited 2019 May 3]. Available from: Scholar
  33. 33.
    Bellen HJ, Levis RW, Liao G, He Y, Carlson JW, Tsang G, et al (2004, June 1) The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167(2):761–781. [Internet] [cited 2019 May 3]. Available from: Scholar
  34. 34.
    Lohr D, Venkov P, Zlatanova J (1995) Transcriptional regulation in the yeast GAL gene family: a complex genetic network. FASEB J 9(9):777–787. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  35. 35.
    Giniger E, Varnum SM, Ptashne M (1985) Specific DNA binding of GAL4, a positive regulatory protein of yeast. Cell 40(4):767–774. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  36. 36.
    Brand AH, Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118(2):401–LP-415. [Internet]. Available from: Scholar
  37. 37.
    McGuire SE, Mao Z, Davis RL (2004) Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Sci Signal 2004(220):pl6–pl6. [Internet]. Available from: Scholar
  38. 38.
    Bier E, Harrison MM, O’Connor-Giles KM, Wildonger J (2018) Advances in engineering the Fly genome with the CRISPR-Cas system. Genetics 208:1):1–1)18. [Internet] [cited 2019 May 3]. Available from: Scholar
  39. 39.
    Heigwer F, Port F, Boutros MRNA (2018) Interference (RNAi) screening in drosophila. Genetics 208(3):853–874. [Internet] [cited 2019 May 3]. Available from: Scholar
  40. 40.
    Lee P-T, Zirin J, Kanca O, Lin W-W, Schulze KL, Li-Kroeger D et al (2018) A gene-specific T2A-GAL4 library for Drosophila. elife. [Internet]; 7. Available from:
  41. 41.
    Lee PT, Zirin J, Kanca O, Lin WW, Schulze KL, Li-Kroeger D et al (2018) A gene-specific T2A-GAL4 library for drosophila. elife 7(1993):1–24Google Scholar
  42. 42.
    del Valle Rodríguez A, Didiano D, Desplan C (2011) Power tools for gene expression and clonal analysis in Drosophila. Nat Methods 9(1):47–55PubMedCrossRefGoogle Scholar
  43. 43.
    Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194(4260):23–28. [Internet]. Oct 1 [cited 2019 Apr 28]. Available from: Scholar
  44. 44.
    Baba Y, Ishimoto T, Kurashige J, Iwatsuki M, Sakamoto Y, Yoshida N et al (2016) Epigenetic field cancerization in gastrointestinal cancers. Cancer Lett 375(2):360–366. [Internet]. Available from: Scholar
  45. 45.
    Mohan M, Jagannathan N (2014) Oral field cancerization: an update on current concepts. Oncol Rev 8(1):13–19CrossRefGoogle Scholar
  46. 46.
    Rhiner C, Moreno E (2009) Super competition as a possible mechanism to pioneer precancerous fields. Carcinogenesis 30(5):723–728PubMedCrossRefGoogle Scholar
  47. 47.
    Xu T, Rubin GM (1993) Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117:1223–1237. [Internet] [cited 2019 May 1]. Available from: Scholar
  48. 48.
    Theodosiou NA, Xu T (1998) Use of FLP/FRT system to study drosophila development. Methods 14(4):355–365. [Internet] [cited 2019 Feb 26]. Available from: Scholar
  49. 49.
    Harrison DA, Perrimon N (1993) Simple and efficient generation of marked clones in Drosophila. Curr Biol 3(7):424–433. [Internet] [cited 2019 Apr 29]. Available from: Scholar
  50. 50.
    Zong H, Espinosa JS, Su HH, Muzumdar MD, Luo L (2005) Mosaic analysis with double markers in mice. Cell 121(3):479–492. [Internet] [cited 2019 May 1]. Available from: Scholar
  51. 51.
    Muzumdar MD, Luo L, Zong H (2007) Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM). Proc Natl Acad Sci U S A 104(11):4495–4500. [Internet] [cited 2019 May 1]. Available from: Scholar
  52. 52.
    Wang W, Warren M, Bradley A (2007) Induced mitotic recombination of p53 in vivo. Proc Natl Acad Sci U S A 104(11):4501–4505. [Internet] [cited 2019 May 1]. Available from: Scholar
  53. 53.
    Sun L, Wu X, Han M, Xu T, Zhuang Y (2008) A mitotic recombination system for mouse chromosome 17. Proc Natl Acad Sci U S A 105(11):4237–4241. [Internet] [cited 2019 May 1]. Available from: Scholar
  54. 54.
    Lee T, Luo L (2001) Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development. Trends Neurosci 24(5):251–254PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Golic KG, Lindquist S (1989) The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell 59(3):499–509. [Internet]. 3 [cited 2019 Apr 29]. Available from: Scholar
  56. 56.
    Ziosi M, Baena-López LA, Grifoni D, Froldi F, Pession A, Garoia F et al (2010) dMyc functions downstream of yorkie to promote the supercompetitive behavior of hippo pathway mutant cells. PLoS Genet 6(9):e1001140PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Tyler DM, Li W, Zhuo N, Pellock B, Baker NE (2007) Genes affecting cell competition in drosophila. Genetics 175(2):643–657PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Tamori Y, Bialucha CU, Tian AG, Kajita M, Huang YC, Norman M et al (2010) Involvement of Lgl and mahjong/VprBP in cell competition. PLoS Biol 8(7):e1000422PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Tamori Y, Suzuki E, Deng WM (2016) Epithelial tumors originate in tumor hotspots, a tissue-intrinsic microenvironment. PLoS Biol 14(9).. [Internet]. Available from: Scholar
  60. 60.
    Evans CJ, Olson JM, Ngo KT, Kim E, Lee NE, Kuoy E et al (2009) G-TRACE: rapid Gal4-based cell lineage analysis in Drosophila. Nat Methods 6(8):603–605. [Internet] [cited 2019 May 1]. Available from: Scholar
  61. 61.
    Bosch JA, Tran NH, Hariharan IK (2015) CoinFLP: a system for efficient mosaic screening and for visualizing clonal boundaries in Drosophila. Development 142(3):597–606. [Internet] [cited 2019 May 1]. Available from: Scholar
  62. 62.
    Bier E, Harrison MM, O’Connor-Giles KM, Wildonger J (2018) Advances in engineering the Fly genome with the CRISPR-Cas system. Genetics 208(1):1–LP-18. [Internet]. 1. Available from: Scholar
  63. 63.
    Gratz SJ, Harrison MM, Wildonger J, O’Connor-Giles KM (2015) Precise genome editing of drosophila with CRISPR RNA-Guided Cas9. In: Methods in molecular biology, pp 335–348. (Clifton, NJ) [Internet]. [cited 2019 Feb 26]. Available from: Scholar
  64. 64.
    Nakazawa N, Taniguchi K, Okumura T, Maeda R, Matsuno K (2012) A novel Cre/loxP system for mosaic gene expression in the Drosophila embryo. Dev Dyn 241(5):965–974. [Internet] [cited 2019 Feb 26]. Available from: Scholar
  65. 65.
    Siegal ML, Hartl DL (2000) Application of Cre/loxP in Drosophila: Site-Specific Recombination and Transgene Coplacement. In: Developmental biology protocols. Humana Press, New Jersey, pp 487–495. [Internet] [cited 2019 Feb 26].. Available from: Scholar
  66. 66.
    Kerbel RS Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: better than commonly perceived-but they can be improved. Cancer Biol Ther 2(4 Suppl 1):S134–S139. [Internet]. [cited 2019 May 4]. Available from: Scholar
  67. 67.
    Morton CL, Houghton PJ (2007) Establishment of human tumor xenografts in immunodeficient mice. Nat Protoc 2(2):247–250. [Internet] [cited 2019 May 4]. Available from: Scholar
  68. 68.
    Rossi F, Gonzalez C (2015) Studying tumor growth in Drosophila using the tissue allograft method. Nat Protoc 10(10):1525–1534. [Internet]. Available from: Scholar
  69. 69.
    Schlosser T, Willoughby LF, Street IP, Richardson HE, Manning SA, Humbert PO et al (2012) An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery. Dis Model Mech 6(2):521–529PubMedPubMedCentralGoogle Scholar
  70. 70.
    Bell AJ, McBride SMJ, Dockendorff TC (2009) Flies as the ointment : Drosophila modeling to enhance drug discovery. Fly (Austin) 3(1):39–49CrossRefGoogle Scholar
  71. 71.
    Karaiskos N, Wahle P, Alles J, Boltengagen A, Ayoub S, Kipar C et al The Drosophila embryo at single-cell transcriptome resolution. Science 358(6360):194–199. [Internet]. 2017 Oct 13 [cited 2019 May 3]. Available from: Scholar
  72. 72.
    Davie K, Janssens J, Koldere D, De Waegeneer M, Pech U, Kreft Ł et al (2018) A single-cell transcriptome atlas of the aging Drosophila brain. Cell 174(4):982–998.e20. [Internet] [cited 2019 May 3]. Available from: Scholar
  73. 73.
    Croset V, Treiber CD, Waddell S (2018) Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics. Elife [Internet].. [cited 2019 May 3];7. Available from:
  74. 74.
    Ariss MM, Islam ABMMK, Critcher M, Zappia MP, Frolov MV (2018) Single cell RNA-sequencing identifies a metabolic aspect of apoptosis in Rbf mutant. Nat Commun 9(1):5024. [Internet] [cited 2019 May 3]. Available from: Scholar
  75. 75.
    Levitin HM, Yuan J, Sims PA (2018) Single-cell transcriptomic analysis of tumor heterogeneity. Trends Cancer 4(4):264–268. [Internet]. Available from: Scholar
  76. 76.
    Jiang Y, Qiu Y, Minn AJ, Zhang NR (2016) Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing. Proc Natl Acad Sci 113(37):E5528–E5537. [Internet] [cited 2019 Jan 22]. Available from: Scholar
  77. 77.
    Mechler BM, McGinnis W, Gehring WJ (1985) Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. EMBO J 4(6):1551–1557. [Internet]. Available from:, Scholar
  78. 78.
    Knudson AG (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68(4):820–823. [Internet] [cited 2019 May 4]. Available from: Scholar
  79. 79.
    Harris H, Miller OJ, Klein G, Worst P, Tachibana T (1969) Suppression of malignancy by cell fusion. Nature 223(5204):363–368. [Internet] [cited 2019 May 4]. Available from: Scholar
  80. 80.
    Stewart M, Murphy C, Fristrom JW (1972) The recovery and preliminary characterization of X chromosome mutants affecting imaginal discs ofDrosophila melanogaster. Dev Biol 27(1):71–83. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  81. 81.
    Bilder D, Perrimon N (2000) Localization of apical epithelial determinants by the basolateral PDZ protein scribble. Nature 403(6770):676–680. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  82. 82.
    Grzeschik NA, Parsons LM, Richardson HE (2010) Lgl, the SWH pathway and tumorigenesis: it’s a matter of context & competition! Cell Cycle 9(16):3202–3212PubMedCrossRefGoogle Scholar
  83. 83.
    Papagiannouli F, Mechler BM (2004) Refining the role of Lgl , Dlg and Scrib in tumor suppression and beyond : learning from the old time classics. Genet Anal 1(Bilder):182–219Google Scholar
  84. 84.
    Brumby AM, Richardson HE (2003) Scribble mutants cooperate with oncogenic Ras or notch to cause neoplastic overgrowth in Drosophila. EMBO J 22(21):5769–5779PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Pagliarini RA, Xu T (2003) A genetic screen in drosophila for metastatic behavior. Science (80- ) 302(5648):1227–1231. [Internet] [cited 2019 Apr 27]. Available from: Scholar
  86. 86.
    Lai Z-C, Wei X, Shimizu T, Ramos E, Rohrbaugh M, Nikolaidis N et al (2005) Control of cell proliferation and apoptosis by mob as tumor suppressor, Mats. Cell 120(5):675–685. [Internet] [cited 2019 May 3. Available from: Scholar
  87. 87.
    Udan RS, Kango-Singh M, Nolo R, Tao C, Halder G (2003) Hippo promotes proliferation arrest and apoptosis in the Salvador/warts pathway. Nat Cell Biol 5(10):914–920. [Internet] [cited 2019 May 3]. Available from: Scholar
  88. 88.
    Pantalacci S, Tapon N, Léopold P (2003) The Salvador partner hippo promotes apoptosis and cell-cycle exit in Drosophila. Nat Cell Biol 5(10):921–927. [Internet] [cited 2019 May 3]. Available from: Scholar
  89. 89.
    Harvey KF, Pfleger CM, Hariharan IK (2003) The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell 114(4):457–467. [Internet]. [cited 2019 May 3]. Available from: Scholar
  90. 90.
    Tapon N, Harvey KF, Bell DW, Wahrer DCR, Schiripo TA, Haber DA et al (2002) Salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110(4):467–478. [Internet] [cited 2019 May 3]. Available from: Scholar
  91. 91.
    Kango-Singh M, Nolo R, Tao C, Verstreken P, Hiesinger PR, Bellen HJ et al (2002) Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila. Development 129(24):5719–5730. [Internet] [cited 2019 May 3]. Available from: Scholar
  92. 92.
    Xu T, Wang W, Zhang S, Stewart RA, Yu W (1995) Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121(4):1053–1063. [Internet] [cited 2019 May 3]. Available from: Scholar
  93. 93.
    Justice RW, Zilian O, Woods DF, Noll M, Bryant PJ (1995) The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev 9(5):534–546. [Internet] [cited 2019 May 3]. Available from: Scholar
  94. 94.
    Sharma SV, Haber DA, Settleman J (2010) Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents. Nat Rev Cancer 10(4):241–253. [Internet] [cited 2019 May 4]. Available from: Scholar
  95. 95.
    Lovitt CJ, Shelper TB, Avery VM (2014) Advanced cell culture techniques for cancer drug discovery. Biology (Basel) 3(2):345–367. [Internet] [cited 2019 May 4]. Available from: Scholar
  96. 96.
    Scherer WF, Syverton JT, Gey GO (1953) Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J Exp Med 97(5):695–710. [Internet] [cited 2019 May 4]. Available from: Scholar
  97. 97.
    Pandey UB, Nichols CD (2011) Human disease models in Drosophila melanogaster and the role of the Fly in therapeutic drug discovery. Drug Deliv 63(2):411–436Google Scholar
  98. 98.
    Morris EJ, Ji J-Y, Yang F, Di Stefano L, Herr A, Moon N-S et al (2008) E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8. Nature 455(7212):552–556. [Internet] [cited 2019 May 4]. Available from: Scholar
  99. 99.
    Cranston AN, Ponder BAJ (2003) Modulation of medullary thyroid carcinoma penetrance suggests the presence of modifier genes in a RET transgenic mouse model. Cancer Res 63(16):4777–4780. [Internet] [cited 2019 May 4]. Available from: Scholar
  100. 100.
    Smith-Hicks CL, Sizer KC, Powers JF, Tischler AS, Costantini F (2000) C-cell hyperplasia, pheochromocytoma and sympathoadrenal malformation in a mouse model of multiple endocrine neoplasia type 2B. EMBO J 19(4):612–622. [Internet] [cited 2019 May 4]. Available from: Scholar
  101. 101.
    Barkan B, Starinsky S, Friedman E, Stein R, Kloog Y (2006) The Ras inhibitor Farnesylthiosalicylic acid as a potential therapy for Neurofibromatosis type 1. Clin Cancer Res 12(18):5533–5542. [Internet] [cited 2019 May 4]. Available from: Scholar
  102. 102.
    Karim FD, Rubin GM (1998) Ectopic expression of activated Ras1 induces hyperplastic growth and increased cell death in Drosophila imaginal tissues. Development 125:1–9. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  103. 103.
    Bangi E, Murgia C, Teague AGS, Sansom OJ, Cagan RL (2016) Functional exploration of colorectal cancer genomes using Drosophila. Nat Commun 7(May):1–16. [Internet]. Available from: Scholar
  104. 104.
    Ho DM, Pallavi SK, Artavanis-Tsakonas S (2015) The notch-mediated hyperplasia circuitry in Drosophila reveals a Src-JNK signaling axis. Elife [Internet] 4:e05996. Available from:, Scholar
  105. 105.
    Dev R, Wong A, Hui D, Bruera E (2017) The evolving approach to management of cancer cachexia. Oncology (Williston Park) 31(1):23–32. [Internet] [cited 2019 Apr 27]. Available from: Scholar
  106. 106.
    Read RD, Cavenee WK, Furnari FB, Thomas JB (2009) A Drosophila model for EGFR-Ras and PI3K-dependent human glioma. Rulifson E, editor. PLoS Genet 5(2):e1000374. [Internet] [cited 2019 May 4]. Available from: Scholar
  107. 107.
    Ravi M, Ramesh A, Pattabhi A (2017) Contributions of 3D cell cultures for cancer research. J Cell Physiol 232(10):2679–2697. [Internet] [cited 2019 May 4]. Available from: Scholar
  108. 108.
    Figueroa-Clarevega A, Bilder D (2015) Malignant drosophila tumors interrupt insulin signaling to induce cachexia-like wasting. Dev Cell 33(1):47–55. [Internet]. Available from: Scholar
  109. 109.
    Aoyagi T, Terracina KP, Raza A, Matsubara H, Takabe K (2015) Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol 7(4):17–29. [Internet] [cited 2019 Apr 27]. Available from: Scholar
  110. 110.
    Morata G, Ripoll P (1975) Minutes: mutants of drosophila autonomously affecting cell division rate. Dev Biol 42(2):211–221. [Internet] [cited 2019 May 4]. Available from: Scholar
  111. 111.
    Clavería C, Giovinazzo G, Sierra R, Torres M (2013) Myc-driven endogenous cell competition in the early mammalian embryo. Nature 500(7460):39–44. [Internet]. Available from:, Scholar
  112. 112.
    Vincent J-P, Fletcher AG, LAl B-L (2013) Mechanisms and mechanics of cell competition in epithelia. Nat Rev Mol Cell Biol 14(9):581–591. [Internet]. Available from: Scholar
  113. 113.
    Menéndez J, Pérez-Garijo A, Calleja M, Morata G (2010) A tumor-suppressing mechanism in Drosophila involving cell competition and the hippo pathway. Proc Natl Acad Sci U S A 107(33):14651–14656. [Internet]. Available from: Scholar
  114. 114.
    Di Gregorio A, Bowling S, Argeo Rodriguez T (2016) Competition and its role in the regulation of cell fitness from development to cancer. Dev Cell 38:621–634. [Internet] [cited 2019 Apr 27]. Available from: Scholar
  115. 115.
    Johnston LA (2014) Socializing with MYC: cell competition in development and as a model for premalignant cancer. Cold Spring Harb Perspect Med 4(4):1–16CrossRefGoogle Scholar
  116. 116.
    Eichenlaub T, Cohen SM, Herranz H (2016) Cell competition drives the formation of metastatic tumors in a drosophila model of epithelial tumor formation. Curr Biol 26(4):419–427PubMedCrossRefGoogle Scholar
  117. 117.
    Suijkerbuijk SJE, Kolahgar G, Kucinski I, Piddini E (2016) Cell competition drives the growth of intestinal adenomas in Drosophila. Curr Biol 26(4):428–438. [Internet]. Available from: Scholar
  118. 118.
    Harvey K, Tapon N (2007) The Salvador–warts–hippo pathway — an emerging tumour-suppressor network. Nat Rev Cancer 7(3):182–191. [Internet] [cited 2019 May 4]. Available from: Scholar
  119. 119.
    de la Cova C, Abril M, Bellosta P, Gallant P, Johnston LA (2004) Drosophila myc regulates organ size by inducing cell competition. Cell 117(1):107–116. [Internet] [cited 2019 May 4]. Available from: Scholar
  120. 120.
    Moreno E, Basler K (2004) dMyc transforms cells into super-competitors. Cell 117(1):117–129. [Internet] [cited 2019 May 4]. Available from: Scholar
  121. 121.
    Vita M, Henriksson M (2006) The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol 16(4):318–330. [Internet] [cited 2019 May 4]. Available from: Scholar
  122. 122.
    Moreno E (2008) Is cell competition relevant to cancer? Nat Rev Cancer 8(2):141–147. [Internet] [cited 2019 May 4]. Available from: Scholar
  123. 123.
    Ryoo HD, Gorenc T, Steller H (2004) Apoptotic cells can induce compensatory cell proliferation through the JNK and the wingless signaling pathways. Dev Cell 7(4):491–501. [Internet] [cited 2019 May 4]. Available from: Scholar
  124. 124.
    Haynie JL, Bryant PJ (1977) The effects of X-rays on the proliferation dynamics of cells in the imaginal wing disc of Drosophila melanogaster. Wilhelm Roux’s Arch Dev Biol 183(2):85–100. [Internet] [cited 2019 May 4]. Available from: Scholar
  125. 125.
    Friedman R, Friedman R (2016) Drug resistance in cancer: molecular evolution and compensatory proliferation. Oncotarget 7(11):11746–11755. [Internet] [cited 2019 May 4]. Available from: Scholar
  126. 126.
    Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 133(3421):571–573. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  127. 127.
    Tamori Y, Deng WM (2017) Tissue-intrinsic tumor hotspots: terroir for tumorigenesis. Trends Cancer 3(4):259–268. [Internet]. Available from: Scholar
  128. 128.
    Jiang M, Li H, Zhang Y, Yang Y, Lu R, Liu K et al (2017) Transitional basal cells at the squamous–columnar junction generate Barrett’s oesophagus. Nature 550(7677):529–533. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  129. 129.
    Guasch G, Schober M, Pasolli HA, Conn EB, Polak L, Fuchs E (2007) Loss of TGFβ signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell 12(4):313–327. [Internet] [cited 2019 Apr 28]. Available from: Scholar
  130. 130.
    Yang S-A, Portilla J-M, Mihailovic S, Huang Y-C, Deng W-M (2019) Oncogenic notch triggers neoplastic tumorigenesis in a transition-zone-like tissue microenvironment. Dev Cell. [Internet] [cited 2019 Apr 28]. Available from:
  131. 131.
    Calvin DR, Bridges B. The origin of variations in sexual and sex-limited characters. [Internet] [cited 2019 May 6]. Available from:
  132. 132.
    Dobzhansky T (1946) Genetics of natural populations; recombination and variability in populations of Drosophila pseudoobscura. Genetics 31:269–290. [Internet] [cited 2019 May 6]. Available from: Scholar
  133. 133.
    Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA et al (2008) Resistance to therapy caused by intragenic deletion in BRCA2. Nature 451(7182):1111–1115. [Internet] [cited 2019 May 6]. Available from: Scholar
  134. 134.
    Gladstone M, Su TT (2011) Chemical genetics and drug screening in Drosophila cancer models. J Genet Genomics 38(10):497–504. [Internet]. Available from: Scholar
  135. 135.
    Skardal A, Murphy SV, Devarasetty M, Mead I, Kang H-W, Seol Y-J et al (2017) Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci Rep 7(1):8837. [Internet] [cited 2019 May 5]. Available from: Scholar
  136. 136.
    Levine BD, Cagan RL (2016) Drosophila lung Cancer models identify Trametinib plus statin as candidate therapeutic. Cell Rep 14(6):1477–1487. [Internet]. Available from: Scholar
  137. 137.
    Vidal M, Wells S, Ryan A, Cagan R (2005) ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma. Cancer Res 65(9):3538–3541. [Internet] [cited 2019 Feb 20]. Available from: Scholar
  138. 138.
    Bangi E, Garza D, Hild M (2011) In vivo analysis of compound activity and mechanism of action using epistasis in Drosophila. J Chem Biol 4(2):55–68. [Internet]. Available from: Scholar
  139. 139.
    Christofi T, Apidianakis Y (2013) Drosophila and the hallmarks of cancer. In: Adv Biochem Eng Biotechnol. Springer, Berlin/Heidelberg, pp 79–110Google Scholar
  140. 140.
    Grifoni D, Sollazzo M, Fontana E, Froldi F, Pession A (2015) Multiple strategies of oxygen supply in Drosophila malignancies identify tracheogenesis as a novel cancer hallmark. Sci Rep 5:9061. [Internet]. Available from: Scholar
  141. 141.
    Christofi T, Apidianakis Y (2013) Drosophila and the hallmarks of cancer. Adv Biochem Eng Biotechnol 135:79–110PubMedPubMedCentralGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyTulane Cancer Center, LCRC, Tulane University School of MedicineNew OrleansUSA

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