Table 1.

Zebrafish Model

Cancer Model	Modeling Mode	Finding	Reference
Acute lymphocytic leukemia	Transgenic model	They describe the first robust zebrafish pre-B ALL model. This model can reveal differences between MYC-driven pre-B vs T-ALL and be exploited to discover novel pre-B ALL therapies	[110]
Acute myeloid leukemia	Xenograft model	Bone marrow (BM) SOX4 expression could serve as an informative new biomarker for the clinical prognosis of AML patients. And the myeloid-specific expression of SOX4 can induce leukemic phenotype in zebrafish.	[111]
Breast cancer	Xenograft model	Administration of VEGFR inhibitors blocked tumor vascularization and a localized tumor growth but enhanced migration of neutrophils, which in turn promoted tumor invasion and formation of micrometastasis.	[112]
Breast cancer	Xenograft model	Grem1 is a pivotal factor in the reciprocal interplay between breast cancer cells and CAFs, which promotes cancer cell invasion. Targeting Grem1 could be beneficial in the treatment of breast cancer patients with high Grem1 expression.	[67]
Breast cancer	Xenograft model	When the tumor metastases, organ selectivity is driven by both vessel topography and cell-type-dependent extravasation.	[113]
Breast cancer	Xenograft model	SMYD3 is a pivotal SMAD3 cofactor that promotes TGFβ-dependent mesenchymal gene expression and cell migration in breast cancer.	[114]
Breast cancer	Xenograft model	PtPP-loaded and citrate-functionalized HA nanoparticles effectively decrease breast cancer cells survival both in vitro and in vivo in a similar manner to free PtPP.	[115]
Breast cancer and Liver cancer	Xenograft model	Furanodiene showed a markedly synergistic anti-cancer effect when used in combination with 5-FU (5-Fluorouracil) for both human breast cancer MDA-MB-231 cells and human liver cancer BEL-7402 cells xenotransplanted into zebrafish.	[68]
Colon Cancer	Xenograft model	After NR1D1 gene is knocked out, the cell viability is impaired and the formation of micrometastasis is reduced.	[116]
Colorectal cancer	Xenograft model	Endoglin-expressing fibroblasts enhanced colorectal tumor cell infiltration into the liver and decreased survival. And endoglin-expressing CAFs contribute to colorectal cancer progression and metastasis.	[117]
Colorectal cancer	Xenograft model	They found significantly less distant metastasis of ERB-041-treated cells compared to vehicle-treated cells. These results further support ERβ’s anti-tumor role in CRC and the possible use of its agonist in CRC patients.	[60]
Colorectal cancer	Transgenic model	They established a new transgenic zebrafish model with inducible expression of oncogenic krasV12 specifically in the intestine and observed high rates of intestinal tumors.	[61]
Colorectal cancer	Xenograft model	cGAMP inhibited migration through angiogenesis by up-regulating IL-2, TNF-α, and IFN-γ, whereas STAT3 down-regulation inhibited CXCL8, BCL-2, and VEGFA expression.	[118]
Colorectal carcinoma	Xenograft model	Zebrafish xenografts provide remarkable resolution to measure Cetuximab sensitivity. Zebrafish larvae xenografts constitute a promising fast assay for precision medicine, bridging the gap between genotype and phenotype in an in vivo setting.	[119]
Colorectal carcinoma	Xenograft model	L.sulphureus lectin (LSL) almost completely reduced growth, neovascularization and metastasis of human colorectal carcinoma and mouse melanoma. It could be used as safe adjuvant in chemotherapy against colorectal carcinoma and melanoma.	[120]
Colorectal carcinoma	Xenograft model	Crambescidine-816, −830, and −800 disrupt tumor cell adhesion and cytoskeletal integrity promoting the activation of the intrinsic apoptotic signaling, resulting in loss of mitochondrial membrane potential and concomitant caspase-3 cleavage and activation.	[121]
Gastric carcinoma	Xenograft model	The zebrafish xenograft study revealed that administration of Triphala inhibited the xenograft growth and metastasis of transplanted carcinoma cells in vivo.	[56]
Glioblastoma	Xenograft model	Treatment of GBM cells with compound 5 (CMP5) mirrored the effects of PRMT5 knockdown wherein it led to apoptosis of differentiated GBM cells and drove undifferentiated primary patient derived GBM cells into a nonreplicative senescent state.	[122]
Hepatocellular carcinoma	Transgenic model	Mifepristone-inducible and reversible krasV12 transgenic system offers a novel model for understanding hepatocarcinogenesis and a high-throughput screening platform for anti-cancer drugs.	[123]
Hepatocellular carcinoma	Transgenic model	A small Myc target gene set of 16 genes can be used to identify liver tumors due to Myc upregulation. And their zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species.	[124]
Hepatocellular carcinoma	Chemically-induced model	Triploid zebrafish demonstrated an overall increase in latency period in the development of both types of hepatic tumors (hepatocellular carcinomas and adenomas), a finding that can be interpreted as an increased resistance of triploid animals to the carcinogenic effect of N-nitrosodimethylamine.	[125]
Hepatocellular carcinoma	Transgenic model	Metformin can suppress NAFLD-associated HCC progression by decreasing the number of pro-inflammatory macrophages and increasing T cell infiltration.	[126]
Hepatocellular carcinoma	Transgenic model	For tumor-infiltrated neutrophils and macrophages, significantly higher densities in male liver tumors were observed in both xmrk and Myc models. And there was a higher rate of HSC activation accompanied with a higher level of serotonin in male liver tumors.	[127]
Hepatocellular carcinoma	Transgenic model	After krasV12 induction, fibrinogen was up-regulated in oncogenic hepatocytes. They reasoned that fibrinogen may bind to integrin αvβ5 on HSCs to activate HSCs.	[58]
Hepatocellular carcinoma	Transgenic model	Using the Tet-on system for liver-specific expression of fish oncogene xmrk, a hyperactive version of epidermal growth factor receptor homolog, they generated transgenic zebrafish with inducible development of liver cancer.	[128]
Hepatocellular carcinoma	Transgenic model	The distribution of neutrophils and macrophages in HCC was relatively uniform, whereas both types of immune cells were regionally clustered during tumor regression, especially with dominant blood vessel association of macrophage in late regression.	[129]
Hepatocellular carcinoma	Transgenic model	They used zebrafish model to screen for drugs that suppress β-catenin-induced liver growth, and identified two classes of hits, c-Jun N-terminal kinase (JNK) inhibitors and antidepressants, that suppressed this phenotype.	[130]
Hepatocellular carcinoma	Transgenic model	Their study provides an in vivo evidence of the relationship between chronic inflammation and tumorigenesis and reinforces the pivotal role of IL6 in the inflammation-associated hepatocarcinogenesis.	[59]
Hepatocellular carcinoma	Transgenic model	An inflammatory cue from oncogenic hepatocytes upon induction of krasV12 expression causes a rapid recruitment of neutrophils to oncogenic liver and the neutrophils play a promoting role in early hepatocarcinogenesis.	[131]
Leukemia	Transgenic model	Akt pathway activation is sufficient for tumor maintenance, even after loss of survival signals driven by the MYC oncogene.	[50]
Leukemia	Xenograft model	Xenotransplantation models of zebrafish can be used to screen non-teratogenic drugs for leukemia.	[132]
Leukemia	Transgenic model	After screening 26,400 molecules, they identified Lenaldekar (LDK), a compound that eliminates immature T cells in developing zebrafish without affecting the cell cycle in other cell types.	[54]
Leukemia	Xenograft model	Imaging-based LSC xenotransplant screening in zebrafish offers distinct advantages over other animal models and can greatly accelerate the phenotype-driven discovery of anti-LSC agents.	[133]
Liver cancer	Xenograft model	Most toxicants, namely chromium, bisphenol A, lindane, N-nitrosodiethylamine, and PCB126, resulted in increased inflammation and liver tumorigenesis, while arsenic and TCDD had opposite effects.	[134]
Liver cancer	Transgenic model	Halting RhoA signaling could augment Kras-mediated liver overgrowth and tumorigenesis. And activating Rho could be beneficial to suppress Kras-induced liver malignancies.	[135]
Lung cancer	Xenograft model	In the zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells and enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and the zebrafish xenograft model.	[69]
Lung cancer	Xenograft model	BPIQ-induced anti-lung cancer is involved in mitochondrial apoptosis. BPIQ could be a promising anti-lung cancer drug for further applications.	[136]
Lung cancer	Xenograft model	DFIQ exerts anticancer potential in vivo and in vitro and can induce apoptosis. DFIQ-induced apoptosis is associated with lysosome accumulation and the induction of the expression of apoptosis factors, such as Bax, Bad, and tBid.	[70]
Lung cancer	Xenograft model and Transgenic model	Bevacizumab, endostar and apatinib demonstrated remarkable angiogenesis and tumor inhibition effect in the zebrafish model, within the nonlethal dose range. Endostar and bevacizumab showed competitive anti-tumor efficacy.	[137]
Melanoma	Xenograft model	Nodal signaling has a key role in melanoma cell plasticity and tumorigenicity, thereby providing a previously unknown molecular target for regulating tumor progression.	[138]
Melanoma	Transgenic model	Although oncogenic NRAS expression alone was found to be insufficient to promote tumor formation, loss of functional p53 was found to collaborate with NRAS expression in the genesis of melanoma.	[44]
Melanoma	Transgenic model	BRAF activation is sufficient for f-nevus formation, that BRAF activation is among the primary events in melanoma development, and that the p53 and BRAF pathways interact genetically to produce melanoma.	[139]
Melanoma	Xenograft model	The zebrafish model reveals that Spint1a deficiency facilitates oncogenic transformation, regulates the tumor immune microenvironment crosstalk, accelerates the onset of SKCM and promotes metastatic invasion.	[46]
Melanoma	Transgenic model	In an adult model of chronic wounding in zebrafish, they show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation.	[140]
Melanoma	Transgenic model	Transgenic THOR knockout produced fertilization defects in zebrafish and also conferred a resistance to melanoma onset. Likewise, ectopic expression of human THOR in zebrafish accelerated the onset of melanoma.	[141]
Melanoma	Xenograft model	Overexpression of bcl‐xL protein is able to enhance melanoma cell angiogenesis through increasing chemokine CXCL8 secretion. They demonstrate that this feature is associated with the increased ability of bcl‐xL overexpressing cells to enhance invasion in vivo.	[47]
Melanoma	Xenograft model	Employing in vivo imaging coupled with 3D reconstruction, they monitored the interactions between cancer cells and the external surface of zebrafish vessels. And they found that melanoma cells spread along the abluminal vascular surfaces.	[45]
Melanoma	Xenograft model	Combined MEK/autophagy inhibition reduced the invasive and metastatic potential of MEKi-resistant cells in an in vivo zebrafish xenograft.	[142]
Pancreatic cancer	Xenograft model	Xenografts of primary human tumors showed invasiveness and micrometastasis formation within 24 hours after transplantation, which was absent when non-tumor tissue was implanted.	[143]
Rhabdomyosarcoma	Transgenic model	Their novel zebrafish rhabdomyosarcoma model identifies a new PAX3-FOXO1 target, her3/HES3, that contributes to impaired myogenic differentiation and has prognostic significance in human disease.	[144]
T-cell acute lymphoblastic leukemia	Xenograft model	Using a focused chemical genomic approach, they demonstrate that xenografted cell lines harboring mutations in the NOTCH1 and PI3K/AKT pathways respond concordantly to their targeted therapies.	[145]
Thyroid carcinoma	Transgenic model	The expression of TWIST2 plays a role in an early step of BRAFV600E-mediated transformation.	[146]