Melanoma models for the next generation of therapies.

Melanoma models for the next generation of therapies.
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黑色素瘤模型用于下一代治疗。

DOI:
10.1016/j.ccell.2021.01.011
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发表时间:
2021-05-10
期刊:
影响因子:
50.3
通讯作者:
Merlino G
Merlino G
中科院分区:
医学1区
文献类型:
--
作者:
Patton EE;Mueller KL;Adams DJ;Anandasabapathy N;Aplin AE;Bertolotto C;Bosenberg M;Ceol CJ;Burd CE;Chi P;Herlyn M;Holmen SL;Karreth FA;Kaufman CK;Khan S;Kobold S;Leucci E;Levy C;Lombard DB;Lund AW;Marie KL;Marine JC;Marais R;McMahon M;Robles-Espinoza CD;Ronai ZA;Samuels Y;Soengas MS;Villanueva J;Weeraratna AT;White RM;Yeh I;Zhu J;Zon LI;Hurlbert MS;Merlino G

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目前缺乏合适的黑色素瘤模型,可用于评估新的治疗方式的疗效。在这里,我们讨论了黑色素瘤模型,包括基因工程小鼠,患者来源的异种移植,斑马鱼,离体和体外模型的最新技术水平。我们还确定了使用此类模型可以解决的五大挑战,包括转移和肿瘤休眠,耐药性,黑色素瘤免疫反应以及衰老和环境暴露对黑色素瘤进展和耐药性的影响。此外,我们还讨论了为罕见的黑色素瘤亚型建立模型的机会,这是一个未满足的关键需求。最后,我们确定了黑色素瘤模型的关键建议,这些模型可以提高临床前测试的准确性并预测临床试验的疗效,以帮助迎来下一代黑色素瘤治疗。
There is a lack of appropriate melanoma models that can be used to evaluate the efficacy of novel therapeutic modalities. Here, we discuss the current state of the art of melanoma models including genetically engineered mouse, patient-derived xenograft, zebrafish, and ex vivo and in vitro models. We also identify five major challenges that can be addressed using such models, including metastasis and tumor dormancy, drug resistance, the melanoma immune response, and the impact of aging and environmental exposures on melanoma progression and drug resistance. Additionally, we discuss the opportunity for building models for rare subtypes of melanomas, which represent an unmet critical need. Finally, we identify key recommendations for melanoma models that may improve accuracy of preclinical testing and predict efficacy in clinical trials, to help usher in the next generation of melanoma therapies.
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