Patient-derived tumor xenograft model to guide the use of BRAF inhibitors in metastatic melanoma
作者： Pierre Guerreschi , Camille Scalbert , Ahmad Qassemyar , Jerome Kluza , Laura Ravasi
DOI: 10.1097/CMR.0B013E328363ED92
关键词:
摘要: Recently, the BRAF V600 inhibitor, vemurafenib, has revolutionized therapeutic management of metastatic melanoma. However, adverse effects and onset resistance are frequently observed, limiting efficacy this treatment. Patient-derived tumor xenografts (PDTX) engrafted in immunocompromised mice have been proposed as valuable preclinical models that can predict clinical response to treatments. Here, we established a PDTX model V600E melanoma useful for testing vemurafenib. First, validated stability was similar original with respect histology, immunohistochemistry, mutational status, fluorine-18 fluorodeoxyglucose ([(18)F]FDG)-PET/computed tomography (CT). Next, sensitivity vemurafenib determined by growth inhibition decreased standardized uptake value on [(18)F]FDG-PET/CT. Finally, result, using personalized PDTX, allowed successful rechallenge patient who administered lower dose because events. Overall, found provides 'real-time' results an animal phenocopies biology expected responses Thus, 'coclinical' trial help guide treatment
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