Covid-19 Research

Review Article

Zebrafish as a Versatile Model for Cancer Research: Insights from In vitro and In vivo Studies

Journal of Biomedical Research & Environmental Sciences article abstract with citation details, DOI, publication dates, subject areas, full text links, and references.

View DOI Submit Manuscript

Article Details

Publication record, authors, dates, abstract, and full text access.

Open Access
Article Type Review Article
Subject Biology Group
OCLC JBRES Record
Saili Paul and Anisur Rahman Khuda-Bukhsh*
Issue: Volume6-Issue10
Pages: 1424-1431
Received: 2025-09-29
Accepted: 2025-10-09
Published: 2025-10-10

Abstract

Rodent models have provided critical insights into the developmental biology of cancer cells and host responses to transformation. However, mortality from several malignancies remains high, underscoring the need for alternative animal models that allow the integrated study of cancer cell biology, developmental processes, and therapeutic interventions. The zebrafish has emerged as a powerful model owing to its rapid development, tractable genetics, suitability for in vivo imaging, and compatibility with chemical screening.

Multiple approaches-including genetic, xenograft, and chemical models- have been established in zebrafish to investigate alterations in molecular pathways, gene functions during cancer progression, and to evaluate novel anticancer agents. In particular, zebrafish xenograft models provide a low-cost, high-throughput platform that can be rapidly established with minimal sample requirements, making them highly attractive materials for cancer research. These models have been instrumental in exploring tumor proliferation, metastasis, and angiogenesis, while also enabling the study of drug pharmacokinetics, tumor–microenvironment interactions, and the prediction of personalized treatment efficacy.

Collectively, zebrafish models represent a versatile and translationally relevant system for studying tumor biology and accelerating the discovery and evaluation of anticancer therapeutics.

FullText HTML FullText PDF DOI: 10.37871/jbres2198 Crossmark

Certificate of Publication

Certificate of Publication

Copyright

© 2025 Paul S, et al. Distributed under Creative Commons CC-BY 4.0 Creative CommonsAttribution

How to cite this article

Paul S, Khuda AR-Bukhsh. Zebrafi sh as a Versatile Model for Cancer Research: Insights from In vitro and In vivo Studies. J Biomed Res Environ Sci. 2025 Oct 10; 6(10): 1424-1431. doi: 10.37871/jbres2198, Article ID: JBRES2198, Available at: https://www.jelsciences.com/articles/jbres2198.pdf

Subject area(s)

References

  1. Cassar S, Adatto I, Freeman JL, Gamse JT, Iturria I, Lawrence C, Muriana A, Peterson RT, Van Cruchten S, Zon LI. Use of Zebrafish in Drug Discovery Toxicology. Chem Res Toxicol. 2020 Jan 21;33(1):95-118. doi: 10.1021/acs.chemrestox.9b00335. Epub 2019 Nov 16. PMID: 31625720; PMCID: PMC7162671.
  2. Longkumer S, Jamir A, Pankaj PP. Maintenance and Breeding of Zebrafish under Laboratory Conditions for Animal Research. Agricultural Science Digest, 2024 June 44(3): 551-555. doi: 10.18805/ag.D-5599.
  3. Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, McLaren K, Matthews L, McLaren S, Sealy I, Caccamo M, Churcher C, Scott C, Barrett JC, Koch R, Rauch GJ, White S, Chow W, Kilian B, Quintais LT, Guerra-Assunção JA, Zhou Y, Gu Y, Yen J, Vogel JH, Eyre T, Redmond S, Banerjee R, Chi J, Fu B, Langley E, Maguire SF, Laird GK, Lloyd D, Kenyon E, Donaldson S, Sehra H, Almeida-King J, Loveland J, Trevanion S, Jones M, Quail M, Willey D, Hunt A, Burton J, Sims S, McLay K, Plumb B, Davis J, Clee C, Oliver K, Clark R, Riddle C, Elliot D, Threadgold G, Harden G, Ware D, Begum S, Mortimore B, Kerry G, Heath P, Phillimore B, Tracey A, Corby N, Dunn M, Johnson C, Wood J, Clark S, Pelan S, Griffiths G, Smith M, Glithero R, Howden P, Barker N, Lloyd C, Stevens C, Harley J, Holt K, Panagiotidis G, Lovell J, Beasley H, Henderson C, Gordon D, Auger K, Wright D, Collins J, Raisen C, Dyer L, Leung K, Robertson L, Ambridge K, Leongamornlert D, McGuire S, Gilderthorp R, Griffiths C, Manthravadi D, Nichol S, Barker G, Whitehead S, Kay M, Brown J, Murnane C, Gray E, Humphries M, Sycamore N, Barker D, Saunders D, Wallis J, Babbage A, Hammond S, Mashreghi-Mohammadi M, Barr L, Martin S, Wray P, Ellington A, Matthews N, Ellwood M, Woodmansey R, Clark G, Cooper J, Tromans A, Grafham D, Skuce C, Pandian R, Andrews R, Harrison E, Kimberley A, Garnett J, Fosker N, Hall R, Garner P, Kelly D, Bird C, Palmer S, Gehring I, Berger A, Dooley CM, Ersan-Ürün Z, Eser C, Geiger H, Geisler M, Karotki L, Kirn A, Konantz J, Konantz M, Oberländer M, Rudolph-Geiger S, Teucke M, Lanz C, Raddatz G, Osoegawa K, Zhu B, Rapp A, Widaa S, Langford C, Yang F, Schuster SC, Carter NP, Harrow J, Ning Z, Herrero J, Searle SM, Enright A, Geisler R, Plasterk RH, Lee C, Westerfield M, de Jong PJ, Zon LI, Postlethwait JH, Nüsslein-Volhard C, Hubbard TJ, Roest Crollius H, Rogers J, Stemple DL. The zebrafish reference genome sequence and its relationship to the human genome. Nature. 2013 Apr 25;496(7446):498-503. doi: 10.1038/nature12111. Epub 2013 Apr 17. Erratum in: Nature. 2014 Jan 9;505(7482):248. Cooper, James [corrected to Cooper, James D]; Eliott, David [corrected to Elliot, David]; Mortimer, Beverly [corrected to Mortimore, Beverley]; Begum, Sharmin [added]; Lloyd, Christine [added]; Lanz, Christa [added]; Raddatz, Günter [added]; Schuster, Ste. PMID: 23594743; PMCID: PMC3703927.
  4. Stoletov K, Klemke R. Catch of the day: zebrafish as a human cancer model. Oncogene. 2008 Jul 31;27(33):4509-20. doi: 10.1038/onc.2008.95. Epub 2008 Mar 31. PMID: 18372910.
  5. Tobia C, De Sena G, Presta M. Zebrafish embryo, a tool to study tumor angiogenesis. Int J Dev Biol. 2011;55(4-5):505-9. doi: 10.1387/ijdb.103238ct. PMID: 21858773.
  6. Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. Stages of embryonic development of the zebrafish. Dev Dyn. 1995 Jul;203(3):253-310. doi: 10.1002/aja.1002030302. PMID: 8589427.
  7. Teame T, Zhang Z, Ran C, Zhang H, Yang Y, Ding Q, Xie M, Gao C, Ye Y, Duan M, Zhou Z. The use of zebrafish (Danio rerio) as biomedical models. Anim Front. 2019 Jun 25;9(3):68-77. doi: 10.1093/af/vfz020. PMID: 32002264; PMCID: PMC6951987.
  8. Konantz M, Balci TB, Hartwig UF, Dellaire G, André MC, Berman JN, Lengerke C. Zebrafish xenografts as a tool for in vivo studies on human cancer. Ann N Y Acad Sci. 2012 Aug;1266:124-37. doi: 10.1111/j.1749-6632.2012.06575.x. PMID: 22901264.
  9. Huang H, Vogel SS, Liu N, Melton DA, Lin S. Analysis of pancreatic development in living transgenic zebrafish embryos. Mol Cell Endocrinol. 2001 May 25;177(1-2):117-24. doi: 10.1016/s0303-7207(01)00408-7. PMID: 11377827.
  10. Feitsma H, Cuppen E. Zebrafish as a cancer model. Mol Cancer Res. 2008 May;6(5):685-94. doi: 10.1158/1541-7786.MCR-07-2167. PMID: 18505914.
  11. Lam SH, Chua HL, Gong Z, Lam TJ, Sin YM. Development and maturation of the immune system in zebrafish, Danio rerio: a gene expression profiling, in situ hybridization and immunological study. Dev Comp Immunol. 2004 Jan;28(1):9-28. doi: 10.1016/s0145-305x(03)00103-4. PMID: 12962979.
  12. Lee LM, Seftor EA, Bonde G, Cornell RA, Hendrix MJ. The fate of human malignant melanoma cells transplanted into zebrafish embryos: assessment of migration and cell division in the absence of tumor formation. Dev Dyn. 2005 Aug;233(4):1560-70. doi: 10.1002/dvdy.20471. PMID: 15968639.
  13. Huiting LN, Laroche F, Feng H. The Zebrafish as a Tool to Cancer Drug Discovery. Austin J Pharmacol Ther. 2015;3(2):1069. Epub 2015 May 4. PMID: 26835511; PMCID: PMC4731041.
  14. Mimeault M, Batra SK. Emergence of zebrafish models in oncology for validating novel anticancer drug targets and nanomaterials. Drug Discov Today. 2013 Feb;18(3-4):128-40. doi: 10.1016/j.drudis.2012.08.002. Epub 2012 Aug 10. PMID: 22903142; PMCID: PMC3562372.
  15. Xie X, Ross JL, Cowell JK, Teng Y. The promise of zebrafish as a chemical screening tool in cancer therapy. Future Med Chem. 2015;7(11):1395-405. doi: 10.4155/fmc.15.73. PMID: 26230879.
  16. White R, Rose K, Zon L. Zebrafish cancer: the state of the art and the path forward. Nat Rev Cancer. 2013 Sep;13(9):624-36. doi: 10.1038/nrc3589. PMID: 23969693; PMCID: PMC6040891.
  17. Ju B, Chen W, Orr BA, Spitsbergen JM, Jia S, Eden CJ, Henson HE, Taylor MR. Oncogenic KRAS promotes malignant brain tumors in zebrafish. Mol Cancer. 2015 Feb 3;14(1):18. doi: 10.1186/s12943-015-0288-2. PMID: 25644510; PMCID: PMC4320811.
  18. White RM, Sessa A, Burke C, Bowman T, LeBlanc J, Ceol C, Bourque C, Dovey M, Goessling W, Burns CE, Zon LI. Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell. 2008 Feb 7;2(2):183-9. doi: 10.1016/j.stem.2007.11.002. PMID: 18371439; PMCID: PMC2292119.
  19. Pontes KCS, Groenewoud A, Cao J, Ataide LMS, Snaar-Jagalska E, Jager MJ. Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma. Invest Ophthalmol Vis Sci. 2017 Dec 1;58(14):6065-6071. doi: 10.1167/iovs.17-22023. PMID: 29204645.
  20. Yan C, Brunson DC, Tang Q, Do D, Iftimia NA, Moore JC, Hayes MN, Welker AM, Garcia EG, Dubash TD, Hong X, Drapkin BJ, Myers DT, Phat S, Volorio A, Marvin DL, Ligorio M, Dershowitz L, McCarthy KM, Karabacak MN, Fletcher JA, Sgroi DC, Iafrate JA, Maheswaran S, Dyson NJ, Haber DA, Rawls JF, Langenau DM. Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish. Cell. 2019 Jun 13;177(7):1903-1914.e14. doi: 10.1016/j.cell.2019.04.004. Epub 2019 Apr 25. PMID: 31031007; PMCID: PMC6570580.
  21. Blackburn JS, Liu S, Raimondi AR, Ignatius MS, Salthouse CD, Langenau DM. High-throughput imaging of adult fluorescent zebrafish with an LED fluorescence macroscope. Nat Protoc. 2011 Feb;6(2):229-41. doi: 10.1038/nprot.2010.170. Epub 2011 Feb 3. PMID: 21293462; PMCID: PMC3362200.
  22. Cross LM, Cook MA, Lin S, Chen JN, Rubinstein AL. Rapid analysis of angiogenesis drugs in a live fluorescent zebrafish assay. Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):911-2. doi: 10.1161/01.ATV.0000068685.72914.7E. PMID: 12740225.
  23. Zhang L, Alt C, Li P, White RM, Zon LI, Wei X, Lin CP. An optical platform for cell tracking in adult zebrafish. Cytometry A. 2012 Feb;81(2):176-82. doi: 10.1002/cyto.a.21167. Epub 2011 Dec 7. PMID: 22162445; PMCID: PMC6383206.
  24. Hill D, Chen L, Snaar-Jagalska E, Chaudhry B. Embryonic zebrafish xenograft assay of human cancer metastasis. F1000Res. 2018 Oct 22;7:1682. doi: 10.12688/f1000research.16659.2. PMID: 30473782; PMCID: PMC6234738.
  25. Roel M, Rubiolo JA, Guerra-Varela J, Silva SB, Thomas OP, Cabezas-Sainz P, Sánchez L, López R, Botana LM. Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model. Oncotarget. 2016 Dec 13;7(50):83071-83087. doi: 10.18632/oncotarget.13068. PMID: 27825113; PMCID: PMC5347754.
  26. Ghotra VP, He S, van der Horst G, Nijhoff S, de Bont H, Lekkerkerker A, Janssen R, Jenster G, van Leenders GJ, Hoogland AM, Verhoef EI, Baranski Z, Xiong J, van de Water B, van der Pluijm G, Snaar-Jagalska BE, Danen EH. SYK is a candidate kinase target for the treatment of advanced prostate cancer. Cancer Res. 2015 Jan 1;75(1):230-40. doi: 10.1158/0008-5472.CAN-14-0629. Epub 2014 Nov 11. PMID: 25388286.
  27. Naber HP, Drabsch Y, Snaar-Jagalska BE, ten Dijke P, van Laar T. Snail and Slug, key regulators of TGF-β-induced EMT, are sufficient for the induction of single-cell invasion. Biochem Biophys Res Commun. 2013 May 24;435(1):58-63. doi: 10.1016/j.bbrc.2013.04.037. Epub 2013 Apr 22. PMID: 23618854.
  28. Zeng A, Ye T, Cao D, Huang X, Yang Y, Chen X, Xie Y, Yao S, Zhao C. Identify a Blood-Brain Barrier Penetrating Drug-TNB using Zebrafish Orthotopic Glioblastoma Xenograft Model. Sci Rep. 2017 Oct 30;7(1):14372. doi: 10.1038/s41598-017-14766-2. PMID: 29085081; PMCID: PMC5662771.
  29. Chou HL, Lin YH, Liu W, Wu CY, Li RN, Huang HW, Chou CH, Chiou SJ, Chiu CC. Combination Therapy of Chloroquine and C2-Ceramide Enhances Cytotoxicity in Lung Cancer H460 and H1299 Cells. Cancers (Basel). 2019 Mar 15;11(3):370. doi: 10.3390/cancers11030370. PMID: 30884764; PMCID: PMC6468447.
  30. Cha YR, Weinstein BM. Visualization and experimental analysis of blood vessel formation using transgenic zebrafish. Birth Defects Res C Embryo Today. 2007 Dec;81(4):286-96. doi: 10.1002/bdrc.20103. PMID: 18228261.
  31. Brown HK, Schiavone K, Tazzyman S, Heymann D, Chico TJ. Zebrafish xenograft models of cancer and metastasis for drug discovery. Expert Opin Drug Discov. 2017 Apr;12(4):379-389. doi: 10.1080/17460441.2017.1297416. PMID: 28277839.
  32. Lieschke GJ, Trede NS. Fish immunology. Curr Biol. 2009 Aug 25;19(16):R678-82. doi: 10.1016/j.cub.2009.06.068. PMID: 19706273.
  33. Li XY, Huang LT, Wu JQ, He MF, Zhu SH, Zhan P, Lv TF, Song Y. Zebrafish Xenograft Model of Human Lung Cancer for Evaluating Osimertinib Resistance. Biomed Res Int. 2019 Jun 27;2019:3129748. doi: 10.1155/2019/3129748. PMID: 31346515; PMCID: PMC6620834.
  34. Lee SL, Rouhi P, Dahl Jensen L, Zhang D, Ji H, Hauptmann G, Ingham P, Cao Y. Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model. Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19485-90. doi: 10.1073/pnas.0909228106. Epub 2009 Nov 3. PMID: 19887629; PMCID: PMC2780785.
  35. Ban J, Aryee DN, Fourtouna A, van der Ent W, Kauer M, Niedan S, Machado I, Rodriguez-Galindo C, Tirado OM, Schwentner R, Picci P, Flanagan AM, Berg V, Strauss SJ, Scotlandi K, Lawlor ER, Snaar-Jagalska E, Llombart-Bosch A, Kovar H. Suppression of deacetylase SIRT1 mediates tumor-suppressive NOTCH response and offers a novel treatment option in metastatic Ewing sarcoma. Cancer Res. 2014 Nov 15;74(22):6578-88. doi: 10.1158/0008-5472.CAN-14-1736. Epub 2014 Oct 3. PMID: 25281719.
  36. Zhang M, Di Martino JS, Bowman RL, Campbell NR, Baksh SC, Simon-Vermot T, Kim IS, Haldeman P, Mondal C, Yong-Gonzales V, Abu-Akeel M, Merghoub T, Jones DR, Zhu XG, Arora A, Ariyan CE, Birsoy K, Wolchok JD, Panageas KS, Hollmann T, Bravo-Cordero JJ, White RM. Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins. Cancer Discov. 2018 Aug;8(8):1006-1025. doi: 10.1158/2159-8290.CD-17-1371. Epub 2018 Jun 14. PMID: 29903879; PMCID: PMC6192670.
  37. L SW, Lee CH, Lin MS, Chi CW, Chen YJ, Wang GS, Liao KW, Chiu LP, Wu SH, Huang DM, Chen L, Shen YS. ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway. Int J Mol Sci. 2020 Feb 26;21(5):1612. doi: 10.3390/ijms21051612. PMID: 32111101; PMCID: PMC7084801.
  38. Van Driessche A, Kocere A, Everaert H, Nuhn L, Van Herck S, Griffiths G, Fenaroli F, De Geest BG. pH-sensitive hydrazone-linked doxorubicin nanogels via polymeric-activated ester scaffolds: Synthesis, assembly, and in vitro and in vivo evaluation in tumor-bearing zebrafish. Chem Mater 2018;30:8587-8596. doi: 10.1021/acs.chemmater.8b03702.
  39. Welker AM, Jaros BD, An M, Beattie CE. Changes in tumor cell heterogeneity after chemotherapy treatment in a xenograft model of glioblastoma. Neuroscience. 2017 Jul 25;356:35-43. doi: 10.1016/j.neuroscience.2017.05.010. Epub 2017 May 17. PMID: 28526577; PMCID: PMC5555152.
  40. van der Ent W, Burrello C, Teunisse AF, Ksander BR, van der Velden PA, Jager MJ, Jochemsen AG, Snaar-Jagalska BE. Modeling of human uveal melanoma in zebrafish xenograft embryos. Invest Ophthalmol Vis Sci. 2014 Sep 23;55(10):6612-22. doi: 10.1167/iovs.14-15202. PMID: 25249605.
  41. Zheng MW, Zhang CH, Chen K, Huang M, Li YP, Lin WT, Zhang RJ, Zhong L, Xiang R, Li LL, Liu XY, Wei YQ, Yang SY. Preclinical Evaluation of a Novel Orally Available SRC/Raf/VEGFR2 Inhibitor, SKLB646, in the Treatment of Triple-Negative Breast Cancer. Mol Cancer Ther. 2016 Mar;15(3):366-78. doi: 10.1158/1535-7163.MCT-15-0501. Epub 2015 Dec 31. PMID: 26721945.
  42. Peterson RT, Link BA, Dowling JE, Schreiber SL. Small molecule developmental screens reveal the logic and timing of vertebrate development. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):12965-9. doi: 10.1073/pnas.97.24.12965. PMID: 11087852; PMCID: PMC27161.
Publish with JBRES — Peer-reviewed, multidisciplinary Open Access with rapid review, DOI, and global visibility.
Double-Blind CrossRef DOI Discoverable
Submit Manuscript Membership