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.
Highlights
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
We started by selecting several cancer cell lines known to express VEGF-A (Supplementary Table 1) and characterized the corresponding xenografts according to several hallmarks of cancer, including cell proliferation, cell death, metastatic and angiogenic potentials
Whereas Hs578T was derived from a primary breast carcinoma, MDAMB-468 was isolated from a pleural effusion metastasis originated from a primary breast adenocarcinoma
Summary
Average response rates to anti-VEGF therapies, such as bevacizumab, are reduced for most cancers, while incurring in remarkable costs and side effects. 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. Depending on the tumor cells, VEGF-A inhibition can either reduce or induce metastasis This effect was observed in preclinical mouse models and in patient responses to therapy[11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]
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