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Utilizing Zebrafish to Identify Anti-(Lymph)Angiogenic Compounds for Cancer Treatment: Promise and Future Challenges
Kazuhide S Okuda1, Hui Mei Lee1, Vithya Velaithan1
1Drug Discovery, Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.
Abstract:
Cancer metastasis which predominantly occurs through blood and lymphatic vessels, is the leading cause of death in cancer patients. Consequently, several anti-angiogenic agents have been approved as therapeutic agents for human cancers such as metastatic renal cell carcinoma. Also, anti-lymphangiogenic drugs such as monoclonal antibodies VGX-100 and IMC-3C5 have undergone phase I clinical trials for advanced and metastatic solid tumors. Although anti-tumor-associated angiogenesis has proven to be a promising therapeutic strategy for human cancers, this approach is fraught with toxicities and development of drug resistance. This emphasizes the need for alternative anti-(lymph)angiogenic drugs. The use of zebrafish has become accepted as an established model for high-throughput screening, vascular biology, and cancer research. Importantly, various zebrafish transgenic lines have now been generated that can readily discriminate different vascular compartments. This now enables detailed in vivo studies that are relevant to both human physiological and tumor (lymph)angiogenesis to be conducted in zebrafish. This review highlights recent advancements in the zebrafish anti-vascular screening platform and showcases promising new anti-(lymph)angiogenic compounds that have been derived from this model. In addition, this review discusses the promises and challenges of the zebrafish model in the context of anti-(lymph)angiogenic compound discovery for cancer treatment.
Insights
Zebrafish models accelerate the discovery of novel anti-angiogenic and anti-lymphangiogenic compounds for cancer treatment. This review highlights advancements in zebrafish screening platforms and promising drug candidates, addressing challenges in cancer therapy.
Area of Science:
- Vascular Biology
- Cancer Research
- Drug Discovery
Background:
- Cancer metastasis via blood and lymphatic vessels is a major cause of cancer mortality.
- Anti-angiogenic and anti-lymphangiogenic therapies show promise but face toxicity and resistance issues.
- There is a critical need for novel anti-(lymph)angiogenic drugs.
Purpose of the Study:
- To review advancements in zebrafish-based screening platforms for anti-vascular agents.
- To showcase novel anti-(lymph)angiogenic compounds identified using zebrafish models.
- To discuss the potential and challenges of zebrafish in discovering anti-cancer drugs.
Main Methods:
- Utilizing zebrafish transgenic lines to study vascular compartments in vivo.
- High-throughput screening of compounds for anti-angiogenic and anti-lymphangiogenic activity.
- Reviewing recent literature on zebrafish anti-vascular screening platforms and drug discovery.
Main Results:
- Zebrafish models enable detailed in vivo studies of both physiological and tumor (lymph)angiogenesis.
- Promising new anti-(lymph)angiogenic compounds have been identified through zebrafish screening.
- Advancements in zebrafish platforms facilitate efficient drug discovery.
Conclusions:
- Zebrafish serve as a powerful and established model for high-throughput screening in vascular biology and cancer research.
- The zebrafish model offers a promising avenue for discovering alternative anti-(lymph)angiogenic drugs to combat cancer.
- Further development and application of zebrafish platforms can overcome challenges in anti-cancer drug discovery.
