Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients

被引:11
|
作者
Di Franco, Gregorio [1 ]
Usai, Alice [2 ]
Piccardi, Margherita [2 ]
Cateni, Perla [2 ]
Palmeri, Matteo [1 ]
Pollina, Luca Emanuele [3 ]
Gaeta, Raffaele [3 ]
Marmorino, Federica [4 ,5 ]
Cremolini, Chiara [4 ,5 ]
Dente, Luciana [2 ]
Massolo, Alessandro [2 ]
Raffa, Vittoria [2 ]
Morelli, Luca [1 ]
机构
[1] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Gen Surg Unit, Via Paradisa 2, I-56124 Pisa, Italy
[2] Univ Pisa, Dept Biol, SS 12 Abetone & Brennero 4, I-56127 Pisa, Italy
[3] Univ Pisa, Div Surg Pathol, Dept Surg Med Mol Pathol & Crit Area, Via Paradisa 2, I-56124 Pisa, Italy
[4] Azienda Osped Univ Pisana, Unit Med Oncol 2, Via Roma 67, I-56126 Pisa, Italy
[5] Univ Pisa, Dept Translat Res & New Technol Med & Surg, I-56124 Pisa, Italy
关键词
zebrafish avatar; chemosensitivity; preclinical model; colorectal cancer; personalized medicine; TRANSLATIONAL RESEARCH; PLATFORM; THERAPY; HETEROGENEITY; EMBRYOS;
D O I
10.3390/biomedicines10071474
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy regimens used for colorectal cancer patients. zPDXs are generated by xenografting tumor tissues in two days post-fertilization zebrafish embryos. zPDXs were exposed to chemotherapy regimens (5-FU, FOLFIRI, FOLFOX, FOLFOXIRI) for 48 h. We used a linear mixed effect model to evaluate the zPDX-specific response to treatments showing for 4/36 zPDXs (11%), a statistically significant reduction of tumor size compared to controls. We used the RECIST criteria to compare the outcome of each patient after chemotherapy with the objective response of its own zPDX model. Of the 36 patients enrolled, 8 metastatic colorectal cancer (mCRC), response rate after first-line therapy, and the zPDX chemosensitivity profile were available. Of eight mCRC patients, five achieved a partial response and three had a stable disease. In 6/8 (75%) we registered a concordance between the response of the patient and the outcomes reported in the corresponding zPDX. Our results provide evidence that the zPDX model can reflect the outcome in mCRC patients, opening a new frontier to personalized medicine.
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页数:15
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