Zebrafish xenografts as a fast screening platform for bevacizumab cancer therapy

斑马鱼异种移植作为贝伐单抗癌症治疗的快速筛选平台

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作者:Cátia Rebelo de Almeida, Raquel Valente Mendes, Anna Pezzarossa, Joaquim Gago, Carlos Carvalho, António Alves, Vitor Nunes, Maria José Brito, Maria João Cardoso, Joana Ribeiro, Fátima Cardoso, Miguel Godinho Ferreira, Rita Fior

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.

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