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Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities.
Genes & development Pub Date : 2019-10-01 , DOI: 10.1101/gad.329771.119
Florian Rambow 1, 2 , Jean-Christophe Marine 1, 2 , Colin R Goding 3
Affiliation  

An incomplete view of the mechanisms that drive metastasis, the primary cause of cancer-related death, has been a major barrier to development of effective therapeutics and prognostic diagnostics. Increasing evidence indicates that the interplay between microenvironment, genetic lesions, and cellular plasticity drives the metastatic cascade and resistance to therapies. Here, using melanoma as a model, we outline the diversity and trajectories of cell states during metastatic dissemination and therapy exposure, and highlight how understanding the magnitude and dynamics of nongenetic reprogramming in space and time at single-cell resolution can be exploited to develop therapeutic strategies that capitalize on nongenetic tumor evolution.

中文翻译:

黑色素瘤可塑性和表型多样性:治疗障碍和机会。

对驱动转移(癌症相关死亡的主要原因)机制的不完整认识一直是开发有效治疗和预后诊断的主要障碍。越来越多的证据表明,微环境、遗传病变和细胞可塑性之间的相互作用驱动了转移级联反应和对治疗的耐药性。在这里,使用黑色素瘤作为模型,我们概述了转移扩散和治疗暴露期间细胞状态的多样性和轨迹,并强调了如何利用单细胞分辨率的空间和时间非遗传重编程的幅度和动态来开发治疗方法利用非遗传性肿瘤进化的策略。
更新日期:2019-11-01
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