What a tangled web we weave: emerging resistance mechanisms to inhibition of the phosphoinositide 3-kinase pathway.
What a tangled web we weave: emerging resistance mechanisms to inhibition of the phosphoinositide 3-kinase pathway.
复制标题
DOI：
10.1158/2159-8290.cd-13-0063
复制
发表时间：
2013-12
期刊：
影响因子：
28.2
通讯作者：
Cantley LC
中科院分区：
文献类型：
--
作者：
Klempner SJ;Myers AP;Cantley LC
磷脂酰肌醇3-激酶（PI 3 K）途径是癌症中最常见的突变途径之一，并且正在积极寻求作为治疗靶点。尽管PI 3 K通路在癌症中很重要，但对PI 3 K通路靶向治疗的持久反应在单药治疗中并不常见。几种体外和异种移植模型已经阐明了补偿信号传导和基因组变化，这可能限制PI 3 K抑制剂在临床中的治疗效果。对肿瘤信号传导和基因组变化进行前瞻性评价的未来临床试验可能会确定新的耐药机制以及可能从PI 3 K通路抑制剂中获得最大获益的患者子集。
The phosphoinositide 3-kinase (PI3K) pathway is one of the most frequently mutated pathways in cancer, and is actively being pursued as a therapeutic target. Despite the importance of the PI3K pathway in cancer, durable responses to PI3K-pathway targeted therapies are uncommon with monotherapy. Several in vitro and xenograft models have elucidated compensatory signaling and genomic changes which may limit the therapeutic effectiveness of PI3K inhibitors in the clinic. Future clinical trials with prospective evaluation of tumor signaling and genomic changes are likely to identify novel resistance mechanisms as well as subsets of patients who may derive maximal benefit from PI3K pathway inhibitors.