Institut de Recherche en Immunologie et Cancérologie and Department of Pharmacology, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
J Hematol Oncol. 2010 Feb 11;3:8. doi: 10.1186/1756-8722-3-8.
The Ras-dependent Raf/MEK/ERK1/2 mitogen-activated protein (MAP) kinase signaling pathway is a major regulator of cell proliferation and survival. Not surprisingly, hyperactivation of this pathway is frequently observed in human malignancies as a result of aberrant activation of receptor tyrosine kinases or gain-of-function mutations in RAS or RAF genes. Components of the ERK1/2 pathway are therefore viewed as attractive candidates for the development of targeted therapies of cancer. In this article, we briefly review the basic research that has laid the groundwork for the clinical development of small molecules inhibitors of the ERK1/2 pathway. We then present the current state of clinical evaluation of MEK1/2 inhibitors in cancer and discuss challenges ahead.
Ras 依赖性 Raf/MEK/ERK1/2 丝裂原活化蛋白 (MAP) 激酶信号通路是细胞增殖和存活的主要调节剂。毫不奇怪，由于受体酪氨酸激酶的异常激活或 RAS 或 RAF 基因的功能获得性突变，该通路的过度激活经常在人类恶性肿瘤中观察到。因此，ERK1/2 通路的成分被视为开发癌症靶向治疗的有吸引力的候选物。在本文中，我们简要回顾了为 ERK1/2 通路小分子抑制剂的临床开发奠定基础的基础研究。然后，我们介绍了目前在癌症中评估 MEK1/2 抑制剂的临床评价，并讨论了未来的挑战。
