Department of Thoracic Oncology, LungenClinic Grosshansdorf; member of the Airway research center north (ARCN) as part of the German Centre for Lung Research (DZL), Grosshansdorf, Germany.
Division of Hematology/Oncology, UC Davis Comprehensive Cancer Center, Sacramento, USA.
Lancet Respir Med. 2015 Apr;3(4):319-27. doi: 10.1016/S2213-2600(15)00026-0. Epub 2015 Mar 20.
The MAP-kinase pathway, consisting of the kinases RAS, RAF, MEK, and ERK, is crucial for cell proliferation, inhibition of apoptosis, and migration of cells. Direct inhibition of RAS is not yet possible, whereas inhibition of RAF is already established in malignant melanoma and under investigation in non-small-cell lung cancer (NSCLC). Due to their structure and function, the MEK proteins are attractive targets for cancer therapy and are also under investigation in NSCLC. We discuss strategies of targeting the RAS-RAF-MEK-ERK pathway with emphasis on MEK inhibition, either alone or in combination with other targets or conventional chemotherapy.
MAP 激酶途径由 RAS、RAF、MEK 和 ERK 激酶组成，对于细胞增殖、抑制细胞凋亡和细胞迁移至关重要。目前还不能直接抑制 RAS，而 RAF 的抑制已在恶性黑色素瘤中得到证实，并正在非小细胞肺癌（NSCLC）中进行研究。由于 MEK 蛋白的结构和功能，它们成为癌症治疗的有吸引力的靶点，也在 NSCLC 中进行研究。我们讨论了靶向 RAS-RAF-MEK-ERK 途径的策略，重点是 MEK 抑制，无论是单独使用还是与其他靶点或常规化疗联合使用。
