Table 1.
The contribution of zebrafish cancer models to precision oncology
| Cancer type | Model | Transgene/injected cells | Approach | Results | Specific contribution to precision oncology | Ref. |
|---|---|---|---|---|---|---|
| Melanoma | Transgenic line | mitfa:HRAS G12V | Pharmacological test in vivo | Small molecule inhibitors of MEK and PI3K/mTOR suppress the melanocyte hyperplasia phenotype. | In vivo validation of targeted drugs for the treatment of melanoma. | 25 |
| Transgenic line | mitfa:HRAS G12V | In vivo drug screening | Two FDA-approved compounds cooperate with MEK inhibitors to suppress the growth of transformed melanocytes. | Discovery of two new potential drugs for the treatment of melanoma. | 25 | |
| XT | Human uveal melanoma cells generated from primary tumors and metastasis | Pharmacological test in vivo | Targeted inhibition of known pathways by specific drugs is effective in counteracting cancer cells migration and proliferation. | Validation of a zebrafish xenograft model as a drug screening platform for the treatment of melanoma. | 66 | |
| Glioma | Transgenic line | ptf1a:Gal4;UAS:GFP-UAS:DAAkt1 | Pharmacological test in vivo | AKT1/2 inhibitor suppresses gliomagenesis, inhibits cellular proliferation, and induces apoptosis in established gliomas. | In vivo identification of a targeted drug for the treatment of glioma. | 28 |
| XT | Human glioblastoma cells | Pharmacological test in vivo | JNK, ERK, and PI3K inhibitors suppress angiogenesis induced by glioblastoma cells. | In vivo validation of targeted drugs for the treatment of glioblastoma via angiogenesis inhibition. | 73 | |
| XT | Human glioblastoma cells | In vitro drug screening in vivo pharmacological test | A novel small molecule radiation sensitizer enhances the tumor growth-inhibitory effects of ionizing radiation. | Discovery of a new small molecule radiation sensitizer for the treatment of glioblastoma. | 74 | |
| XT | Glioma stem cells (GSCs) isolated from a human glioblastoma cell line | Pharmacological test in vivo | A synthetic compound, Nordy, suppresses angiogenesis, tumor invasion, and proliferation of the zebrafish GSC xenograft. | In vivo validation of a drug targeting GSCs for the treatment of glioblastoma. | 75,76 | |
| XT | Human glioblastoma cells | Pharmacological test in vivo | A drug with a known anti-cancer effect in cell culture inhibits proliferation and invasion in the xenograft model. | Proof of principle for the use of a zebrafish orthotopic xenograft model as a drug screening platform for the treatment of glioblastoma. | 60 | |
| XT | Patient-derived glioma cells | Pharmacological test in vivo | Currently used glioblastoma therapeutics decrease xenotransplant tumor burden and significantly rescue survival. | Validation of a zebrafish orthotopic xenograft model as a drug screening platform for the treatment of glioblastoma. | 9 | |
| Brain pediatric tumors | XT | Mouse ependymoma, glioma, and choroid plexus carcinoma cells | Pharmacological test in vivo | A cytotoxic chemotherapeutic agent (5-fluorouracil) and a tyrosine kinase inhibitor suppress ERBB2-driven gliomas. | Proof of principle for the use of a zebrafish orthotopic xenograft model as a drug screening platform for the treatment of pediatric brain tumors. | 71 |
| Pancreatic cancer | XT | Human pancreatic adenocarcinoma cells | Pharmacological test in vivo | A known small molecule inhibitor, U0126, targeting the KRAS signaling pathway, represses proliferation and migration of cancer cells. | In vivo validation of a targeted drug for the treatment of pancreatic cancer. | 77 |
| Leukemia and lymphoma | WT embryos | — | In vivo drug screening | Chemicals that enhance prostaglandin (PG) E2 synthesis increase HSC numbers. | Development of Prohema, currently in Phase II clinical trials for use in leukemia and lymphoma patients receiving blood transplantations. | 47,48 |
| T-ALL | XT | Patient-derived T-ALL cells | Pharmacological test in vivo | A bone marrow sample derived from a T-ALL patient harboring a NOTCH1 mutation responds to NOTCH1 inhibitor in the zebrafish xenograft model. | Proof of principle for the use of a zebrafish xenotransplantation model as a preclinical platform for a personalized therapy. | 5 |
| Thyroid cancer | Transgenic line | tg:BRAF V600E | Pharmacological test in vivo | Combinatorial treatment with BRAF and MEK inhibitors rescue normal follicular architecture, restore thyroid hormone production, and reduce epithelial mesenchymal transition. | In vivo validation of targeted drugs for the treatment of thyroid cancer. | 49 |
| Hepatocellular carcinoma | Transgenic line | fabp10a:pt-β-catenin | In vivo drug screening | Two c-Jun N-terminal kinase (JNK) inhibitors and two anti-depressants suppress β-catenin-induced liver growth. | Discovery of two classes of potential targeted drugs for the treatment of hepatocellular carcinoma. | 56 |
| Retinoblastoma | XT | Human retinoblastoma cells | Pharmacological test in vivo | Orthotopic xenograft of retinoblastoma cells permits quantitative analysis of cancer cells proliferation and the anti-cancer effect of drugs systemically administered. | Validation of a zebrafish orthotopic xenograft model as a drug screening platform for the treatment of retinoblastoma. | 62 |
| Pancreatic ductal adenocarcinoma (metastasis) | XT | Pancreatic carcinoma cells and fragments of resected tumor tissue | Pharmacological test in vivo | miR-10A suppression by knockdown or retinoid acid receptor antagonists blocks metastasis. | In vivo validation of a new molecular target and anti-metastatic targeted drugs for the treatment of pancreatic cancer. | 8 |
| Prostate cancer (metastasis) | XT | Human prostate cancer cells | Pharmacological test in vivo | Pharmacologic inhibitors of SYK kinase, currently in phase I–II trials for other indications, prevent metastatic dissemination. | In vivo validation of anti-metastatic targeted drugs for the treatment of prostate cancer. | 88 |
| XT | Human prostate cancer cells | Pharmacological test in vivo | The small molecule VPC-18005, targeting ERG, exhibits anti-metastatic activity against prostate cancer cells aberrantly expressing ERG. | In vivo validation of an anti-metastatic targeted drug for the treatment of prostate cancer. | 89 | |
| Melanoma (metastasis) | XT | Mouse melanoma cells | Pharmacological test in vivo | The FDA-approved anti-DNA virus agent cidofovir inhibits metastasis of FGF2-driven tumor cells. | In vivo validation of an anti-metastatic targeted drug for the treatment of melanoma. | 90 |
| Breast cancer (metastasis) | XT | Triple-negative breast cancer cells | Pharmacological test in vivo | Specific inhibition of Arf1 by small molecule LM11 impairs metastatic capability of breast cancer cells. | In vivo validation of a potential anti-metastatic precision oncology treatment for breast cancer patients with ARF1 amplification. | 91 |
| XT | Triple-negative breast cancer cells | Pharmacological test in vivo | Novel compounds designed to antagonize P2 × 7 receptor inhibit invasion of breast cancer cells. | In vivo validation of anti-metastatic targeted drugs for the treatment of breast cancer. | 92 | |
| XT | Triple-negative breast cancer cells | Pharmacological test in vivo | Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1t impairs breast cancer early metastases. | In vivo validation of an anti-metastatic targeted drug for the treatment of breast cancer. | 82 | |
| XT | Primary culture of breast cancer bone metastasis | Xenograft and imaging | Transplanted primary cell behavior reflects the clinical course of the patient’s medical history. | Proof of principle for the use of zebrafish xenograft for the evaluation of cancer patient prognosis. | 7 | |
| Ewing sarcoma (metastasis) | XT | Human Ewing sarcoma cells | Pharmacological test in vivo | The SIRT1/2 inhibitor Tenovin-6 prohibits tumor growth and spread of cancer cells. | In vivo validation of a new molecular target and an anti-metastatic targeted drug for the treatment of Ewing sarcoma. | 93 |
| Gastrointestinal tumors (metastasis) | XT | Tumor explants from pancreas, colon, and stomach carcinoma | Xenograft and imaging | Xenografts of primary human tumors show rapid invasiveness and micrometastasis formation after transplantation in the yolk or organotopically in the liver. | Validation of a zebrafish xenotransplantation model as a platform for the analysis of metastatic behavior of primary human tumor specimen. | 6 |
A summary of studies described in this review that exemplify the utility of zebrafish cancer models in precision oncology research. Contributions of each model to the precision oncology field have been highlighted
XT xenotransplantation, T-ALL T-cell acute lymphoblastic leukemia