一个人黑色素瘤的体内鸟模型,以进行快速和强大的临床前研究。
An in vivo avian model of human melanoma to perform rapid and robust preclinical studies.
发表日期:2023 Jan 24
作者:
Loraine Jarrosson, Stéphane Dalle, Clélia Costechareyre, Yaqi Tang, Maxime Grimont, Maud Plaschka, Marjorie Lacourrège, Romain Teinturier, Myrtille Le Bouar, Delphine Maucort-Boulch, Anaïs Eberhardt, Valérie Castellani, Julie Caramel, Céline Delloye-Bourgeois
来源:
EMBO Molecular Medicine
摘要:
携带BRAFV600基因突变的转移性黑色素瘤患者可以使用BRAF和MEK抑制剂(BRAFi/MEKi)联合治疗,但天生和后天的耐药性总是会发生的。预测患者对靶向治疗的反应对指导临床决策至关重要。我们在这里描述了一种高效的患者来源异种移植模型的开发,采用鸟胚作为宿主(AVI-PDXTM),并适应患者黑色素瘤活检组织。在这个体内模式中,我们描绘了患者样本在胚胎皮肤内快速、可重复的肿瘤移植,以保留关键的分子和表型特征。我们展示了在这些AVI-PDXTM中,对BRAFi/MEKi的敏感性和耐药性可以可靠地进行建模,以及与其他药物的协同作用。我们进一步提供了概念证明,AVI-PDXTM模拟了黑色素瘤患者对BRAFi/MEKi的反应多样性,在几天内得到了验证,从而使其成为个性化药物筛选的有价值工具,并用于评估新的联合策略。© 2023作者。根据CC BY 4.0许可条款发表。
Metastatic melanoma patients carrying a BRAFV600 mutation can be treated with a combination of BRAF and MEK inhibitors (BRAFi/MEKi), but innate and acquired resistance invariably occurs. Predicting patient response to targeted therapies is crucial to guide clinical decision. We describe here the development of a highly efficient patient-derived xenograft model adapted to patient melanoma biopsies, using the avian embryo as a host (AVI-PDXTM ). In this in vivo paradigm, we depict a fast and reproducible tumor engraftment of patient samples within the embryonic skin, preserving key molecular and phenotypic features. We show that sensitivity and resistance to BRAFi/MEKi can be reliably modeled in these AVI-PDXTM , as well as synergies with other drugs. We further provide proof-of-concept that the AVI-PDXTM models the diversity of responses of melanoma patients to BRAFi/MEKi, within days, hence positioning it as a valuable tool for the design of personalized medicine assays and for the evaluation of novel combination strategies.© 2023 The Authors. Published under the terms of the CC BY 4.0 license.