RAF-MEK-ERK信号通路：靶向ERK以克服有效癌症治疗的障碍。
The RAF-MEK-ERK pathway: targeting ERK to overcome obstacles to effective cancer therapy.
作者信息
Yu Zutao, Ye Shiqi, Hu Gaoyun, Lv Meng, Tu Zhijun, Zhou Kun, Li Qianbin
机构信息
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, 410013, Changsha, Hunan, China.
出版信息
Future Med Chem. 2015;7(3):269-89. doi: 10.4155/fmc.14.143.
AIM
Currently, dozens of BRAF inhibitors and MEK inhibitors targeting RAF-MEK-ERK pathway have been introduced into clinical trials for cancer therapy. However, after 6-8 months of initial response, acquired drug resistance among the majority of those treated patients sharply diminished their clinical efficacy.
DISCUSSION
Important mechanisms responsible for acquired resistance of BRAF inhibitors and MEK inhibitors have been elucidated. Continually, ERK1/2 locates in the critical position and features unique characteristics, such as activating hundreds of substrates, participating in feedback regulation, being catalyzed by MEK specifically and no acquired resistant mutation.
CONCLUSION
Taking in account the inspiring outcomes of ERK inhibitors in preclinical research, ERK1/2 might be the optimal target to overcome acquired drug resistance in RAF-MEK-ERK pathway.
目的
目前，数十种靶向RAF-MEK-ERK通路的BRAF抑制剂和MEK抑制剂已被引入癌症治疗的临床试验。然而，在初始反应6-8个月后，大多数接受治疗的患者出现获得性耐药，这大幅降低了它们的临床疗效。
讨论
已阐明BRAF抑制剂和MEK抑制剂获得性耐药的重要机制。持续地，ERK1/2处于关键位置并具有独特特征，例如激活数百种底物、参与反馈调节、由MEK特异性催化且无获得性耐药突变。
结论
考虑到ERK抑制剂在临床前研究中令人鼓舞的结果，ERK1/2可能是克服RAF-MEK-ERK通路中获得性耐药的最佳靶点。
Zotero 插件