Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi e A. Lanzara", Università degli Studi della Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Napoli, Italy.
Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi e A. Lanzara", Università degli Studi della Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Napoli, Italy.
Cancer Treat Rev. 2017 Feb;53:61-69. doi: 10.1016/j.ctrv.2016.12.001. Epub 2016 Dec 30.
The mitogen-activated protein kinases (MAPKs) mediate intracellular signals activated by a wide variety of extracellular stimuli. The activation of the RAS-RAF-MEK-MAPK cascade culminates in the regulation of gene transcription promoting cancer cell proliferation, survival, migration and angiogenesis. MEK (mitogen-activated protein kinase kinase-MAPKK) 1/2 is a transducer of the growth factor receptor-RAS-RAF-MAPK signalling cascade and plays a relevant role in development and progression of human cancers, such as colorectal cancer (CRC), non small cell lung cancer (NSCLC). Direct inhibition of MEK is a promising strategy and several inhibitors are currently under evaluation in clinical trials showing initial clinical activity in different tumours. MEK activation, by different genetic mechanisms, has been described for both intrinsic and acquired resistance to drugs targeting the EGFR (Epidermal Growth Factor Receptor)-RAS-RAF pathway in CRC, NSCLC. Combination therapies with chemotherapy and/or with molecular targeted agents are warranted and biomarkers studies are needed to identify those tumours dependent on MEK signalling.
丝裂原活化蛋白激酶（MAPKs）介导了由多种细胞外刺激激活的细胞内信号。RAS-RAF-MEK-MAPK 级联的激活最终调节促进癌细胞增殖、存活、迁移和血管生成的基因转录。MEK（丝裂原活化蛋白激酶激酶-MAPKK）1/2 是生长因子受体-RAS-RAF-MAPK 信号转导级联的转导物，在人类癌症的发展和进展中发挥着重要作用，如结直肠癌（CRC）、非小细胞肺癌（NSCLC）。MEK 的直接抑制是一种很有前途的策略，目前有几种抑制剂正在临床试验中进行评估，在不同的肿瘤中显示出初步的临床活性。在 CRC 和 NSCLC 中，针对 EGFR（表皮生长因子受体）-RAS-RAF 通路的药物的内在和获得性耐药中，通过不同的遗传机制描述了 MEK 的激活。需要联合化疗和/或分子靶向药物进行联合治疗，并需要进行生物标志物研究，以确定那些依赖于 MEK 信号的肿瘤。
