Targeting the ERK signaling pathway in cancer therapy
Targeting the ERK signaling pathway in cancer therapy
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DOI：
10.1080/07853890600551037
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Pouyssegur, J
中科院分区：
文献类型：
--
作者：
Kohno, M;Pouyssegur, J
细胞外信号调节激酶（ERK）信号通路是控制多种细胞过程如增殖、存活、分化和运动的主要决定因素。该途径通常在人类肿瘤中上调，因此代表了抗癌药物开发的有吸引力的靶点。由于其在获得复杂恶性表型中的多重作用，预期ERK途径的特异性阻断不仅导致抗增殖作用，而且导致肿瘤细胞中的抗转移和抗血管生成作用。最近，已经开发了靶向ERK通路组分的有效小分子抑制剂。其中BAY 43-9006（Raf抑制剂）、PD 184352、PD 0325901和ARRY-142886（MEK 1/2抑制剂）已进入临床试验阶段。我们简要讨论了ERK通路抑制剂（细胞生长抑制剂）和常规抗癌药物（细胞毒性药物）的组合为开发新的抗癌化疗策略提供了良好基础的可能性。
The extracellular signal-regulated kinase (ERK) signaling pathway is a major determinant in the control of diverse cellular processes such as proliferation, survival, differentiation and motility. This pathway is often up-regulated in human tumors and as such represents an attractive target for the development of anticancer drugs. Because of its multiple roles in the acquisition of a complex malignant phenotype, specific blockade of the ERK pathway is expected to result in not only an anti-proliferative effect but also in anti-metastatic and anti-angiogenic effects in tumor cells. Recently potent small-molecule inhibitors targeting the components of the ERK pathway have been developed. Among them, BAY 43-9006 (Raf inhibitor), and PD184352, PD0325901 and ARRY-142886 (MEK1/2 inhibitors) have reached the clinical trial stage. We briefly discuss the possibility that combination of ERK pathway inhibitors (cytostatic agents) and conventional anticancer drugs (cytotoxic agents) provides an excellent basis for the development of new chemotherapeutic strategies against cancer.