Related Experiment Video
Updated: Dec 18, 2025
Drug Screening of Primary Patient Derived Tumor Xenografts in Zebrafish
Published on: April 10, 2020
Zebrafish xenografts as a fast screening platform for bevacizumab cancer therapy
Cátia Rebelo de Almeida1, Raquel Valente Mendes1, Anna Pezzarossa1
1Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038, Lisbon, Portugal.
Abstract:
Despite promising preclinical results, average response rates to anti-VEGF therapies, such as bevacizumab, are reduced for most cancers, while incurring in remarkable costs and side effects. Currently, there are no biomarkers available to select patients that can benefit from this therapy. Depending on the individual tumor, anti-VEGF therapies can either block or promote metastasis. In this context, an assay able to predict individual responses prior to treatment, including the impact on metastasis would prove of great value to guide treatment options. Here we show that zebrafish xenografts are able to reveal different responses to bevacizumab in just 4 days, evaluating not only individual tumor responses but also the impact on angiogenesis and micrometastasis. Importantly, we perform proof-of-concept experiments where clinical responses in patients were compared with their matching zebrafish Patient-Derived Xenografts - zAvatars, opening the possibility of using the zebrafish model to screen bevacizumab therapy in a personalized manner.
Insights
This study introduces a zebrafish xenograft assay to predict individual patient responses to bevacizumab (anti-VEGF therapy) within four days. This novel approach assesses tumor response, angiogenesis, and metastasis, paving the way for personalized cancer treatment selection.
Area of Science:
- Oncology
- Translational Medicine
- Zebrafish Models
Background:
- Anti-VEGF therapies like bevacizumab show limited efficacy and high costs, with no biomarkers for patient selection.
- Tumor response to anti-VEGF agents varies, potentially impacting metastasis, necessitating predictive tools.
- Current treatment selection lacks personalization, leading to suboptimal outcomes and side effects.
Purpose of the Study:
- To develop and validate a rapid assay for predicting individual patient responses to bevacizumab.
- To evaluate the assay's ability to assess tumor growth, angiogenesis, and metastatic potential.
- To establish a proof-of-concept for personalized anti-VEGF therapy screening using zebrafish patient-derived xenografts (zAvatars).
Main Methods:
- Establishment of zebrafish xenografts using patient-derived tumor cells.
- Treatment of xenografts with bevacizumab and assessment of tumor response, angiogenesis, and micrometastasis within 4 days.
- Comparison of zebrafish xenograft responses with matched patient clinical outcomes.
Main Results:
- Zebrafish xenografts accurately predicted individual responses to bevacizumab in 4 days.
- The assay effectively evaluated tumor response, angiogenesis, and impact on micrometastasis.
- Proof-of-concept experiments demonstrated a correlation between zAvatar response and patient clinical outcomes.
Conclusions:
- Zebrafish xenografts offer a rapid and effective platform for predicting bevacizumab efficacy and metastatic potential.
- This zAvatar model holds promise for personalized screening of anti-VEGF therapies in cancer patients.
- The developed assay could guide personalized treatment decisions, improving patient outcomes and reducing healthcare costs.
