论文标题
人类抗原R作为癌细胞持久性和可塑性网络中的可行的超级枢纽
The human antigen R as an actionable super-hub within the network of cancer cell persistency and plasticity
论文作者
论文摘要
在这篇观点文章中，提出了一种以临床启发的表型驱动的实验方法来解决固体癌对小分子靶向疗法的适应性反应的挑战。得出了条件列表，包括对细胞可塑性的实验定量评估和基于信息理论的体内依赖性检测，以发现能够在多个级别的出现塑性分化分化较慢的慢增长细胞的出现的转录后可药物机制。在BRAFV600-黑色素瘤对BRAF抑制作用的适应性反应的示例案例中，作者自己的工作说明了这种方法。基于床位的床位和返回基准的努力导致了一种治疗策略，其中抑制了翻译抑制剂（步态）复合物的基线活性（步态）复杂的抑制剂，在RNA固定蛋白HUR的表达不足中导致细胞中少数细胞的抑制作用，导致细胞的抑制作用，这会导致细胞的抑制作用，这会导致对塑料的抑制作用，从而涉及较慢的细胞的抑制作用。建议采用类似的方法来验证我们试图调节的其他机制，以克服现代癌症治疗的这一复杂挑战。
In this perspective article, a clinically inspired phenotype-driven experimental approach is put forward to address the challenge of the adaptive response of solid cancers to small-molecule targeted therapies. A list of conditions is derived, including an experimental quantitative assessment of cell plasticity and an information theory-based detection of in vivo dependencies, for the discovery of post-transcriptional druggable mechanisms capable of preventing at multiple levels the emergence of plastic dedifferentiated slow-proliferating cells. The approach is illustrated by the author's own work in the example case of the adaptive response of BRAFV600-melanoma to BRAF inhibition. A bench-to-bedside and back to bench effort leads to a therapeutic strategy in which the inhibition of the baseline activity of the interferon-gamma-activated inhibitor of translation (GAIT) complex, incriminated in the expression insufficiency of the RNA-binding protein HuR in a minority of cells, results in the suppression of the plastic, intermittently slow-proliferating cells involved in the adaptive response. A similar approach is recommended for the validation of other classes of mechanisms that we seek to modulate to overcome this complex challenge of modern cancer therapy.
