Zebrafish PDX Model related Service for Live Biotherapeutics Drug Discovery

Background

To determine the safety and efficacy of new anti-cancer drugs, extensive testing is needed in animal models. Exploring the mechanism of tumor angiogenesis and developing anti-angiogenic drugs to inhibit tumor angiogenesis are two important aspects of tumor treatment research. The zebrafish patient-derived xenograft (zPDX) model provides valuable tumor molecular biology information and personalized treatment plans for different types of cancer patients, playing a crucial role in evaluating the effectiveness of anticancer drugs and identifying biomarkers for drug sensitivity and resistance. Zebrafish can be used for human PDX, providing a simple and rapid method for detecting the metastatic behavior of primary cancer cells.

To develop new treatments, zebrafish have proven to be in vivo for studying human cancer biology and have become a top model organism. An immunodeficient adult zebrafish strain lacking T, B, and natural killer (NK) cells could be used to model xenotransplantation to investigate new treatments. Tumor implantation in zebrafish has become an emerging model platform for cancer research. The implanted cancer cells include patient-derived primary cells and laboratory cell lines, and the development of cancer models in zebrafish contributes to the development of precision oncology, as well as the advantages and feasibility of direct clinical applications.

Fig.1 Generation and application of zebrafish models in cancer research.^{1, 3}

PDX Models Services for Anticancer Therapy Studies

Zebrafish has proven to be a good model for studying tumorigenesis and invasion of human breast and prostate cancers, as well as hepatocellular carcinoma (HCC). Transgenic lines of zebrafish with fluoroscopically labeled tissues have been established to provide new insights into cancer cell growth, spread, and the tumor microenvironment in real time. Zebrafish embryo xenotransplantation tests have been used for different purposes in the field of cancer:

• Modeling of tumor cells in multiple tumor entities.
• Evaluate the ability of tumor cells to proliferate, spread, or invade.
• To test their angiogenic potential.
• How new chemotherapy drugs affect their metabolism.

The cancer cells implanted in zebrafish come from various types of malignant tumors, such as germ cell tumors, leukemia, lymphoma, melanoma, sarcoma, neuroblastoma, and various epithelial cancers originating from the neuroendocrine system.

Human Cancer Xenograft Transplantation Models in Zebrafish:

• Cell lines

Melanoma, Colorectal cancer, Pancreatic cancer, ovarian cancer, Prostate cancer, Breast cancer, Glioblastoma, Gastric cancer, and Ewing sarcoma.

• PDX

AML blast cells, MM cells from plasma, MM cells from bone marrow, Glioblastoma.

The zebrafish cancer xenograft model is an excellent choice to study tumor progression and test new therapies.

Zebrafish Cancer Models Have Facilitated Precision Oncology Applications

• Using zebrafish as a platform for in vivo drug screening.
• Actionable changes and definitions of therapeutic targets.
• Discovery of tumor biomarkers and genetic signatures as potential diagnostic and prognostic indicators.
• Evaluate the patient prognosis in vivo.
• Direct individualized treatment in real-time.

Advantages of Zebrafish Models

Transplanting human cancer cells into zebrafish is a proven technique that provides an in vivo environment for real-time visualization of cell-cell interactions. In addition, zebrafish PDX could support the discovery of potential targeted anti-cancer therapies, and could also help preclinical studies reduce drug approval times.

• High throughput
• Low-cost
• A real-time in vivo platform for personalized cancer treatment
• Rapid turnaround
• Small space requirements
• Small sample size requirements
• Low doses of the screened drug
• Suitability for in vivo imaging
• Chemical screening
• Adaptable genetics

Fig.2 Unique features of the zebrafish make them powerful candidates for use as cancer patient avatars.^{2, 3}

Frequently Asked Questions

Given the value of zebrafish as a disease model, its power as a tool in precision oncology is becoming increasingly appreciated and applications are dawning. Would you like to know more about a specific study or drug that has been evaluated using Zebrafish PDX models? Creative Biolabs has built a zebrafish technology platform to evaluate drugs and help you advance your drug development, please do not hesitate to contact us, our team of experts will be happy to help you with customized solutions.

References

1. Singhal, Sharad S., et al. "Recent Advancement in Breast Cancer Research: Insights from Model Organisms—Mouse Models to Zebrafish." Cancers 15.11 (2023): 2961.
2. Al-Hamaly, Majd A., et al. "Zebrafish cancer avatars: A translational platform for analyzing tumor heterogeneity and predicting patient outcomes." International Journal of Molecular Sciences 24.3 (2023): 2288.
3. Distributed under Open Access license CC BY 4.0, without modification.

For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.