How Compensatory Mechanisms and Adaptive Rewiring Have Shaped Our Understanding of Therapeutic Resistance in Cancer.
How Compensatory Mechanisms and Adaptive Rewiring Have Shaped Our Understanding of Therapeutic Resistance in Cancer.
复制标题
补偿机制与适应性神经重塑如何塑造了我们对癌症治疗耐药性的理解
DOI：
10.1158/0008-5472.can-21-3605
复制
发表时间：
2021-12-15
期刊：
影响因子：
11.2
通讯作者：
Zhao JJ
中科院分区：
文献类型：
--
作者：
Bergholz JS;Zhao JJ
肿瘤细胞对靶向治疗的耐药性是临床上常见的严重问题。增加对耐药分子机制的理解对于合理设计和改进有效的药物治疗策略是必要的。O 'Reilly及其同事于2006年在Cancer Research上发表的里程碑式研究为非基因组适应性重新布线和补偿机制提供了有价值的见解，这些机制负责介导对PI 3 K-AKT-mTOR通路的靶向抑制的抵抗，以及肿瘤细胞如何通过负反馈回路调节信号通路。这些发现已被证明是指导目前开发有效组合治疗的基础，并为旨在了解细胞信号传导复杂性的研究提供了蓝图。
Therapeutic resistance to targeted therapies by tumor cells is a common and serious problem in the clinic. Increased understanding of the molecular mechanisms that underly resistance is necessary for the rational design and improvement of effective pharmacological treatment strategies. The landmark study by O’Reilly and colleagues published in Cancer Research in 2006 provided valuable insights into non-genomic adaptive rewiring and compensatory mechanisms responsible for mediating resistance to targeted inhibition of the PI3K-AKT-mTOR pathway, and how tumor cells regulate signaling pathways via negative feedback loops. These findings have proven fundamental for guiding current efforts to develop effective combination treatments, and provided a blueprint for research studies aimed at understanding the intricacies of cellular signaling.