Department of Biology and the Cancer Research Program, JLC-Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA.
Future Med Chem. 2011 Oct;3(14):1787-808. doi: 10.4155/fmc.11.121.
The RAS oncogenes (HRAS, NRAS and KRAS) comprise the most frequently mutated class of oncogenes in human cancers (33%), thus stimulating intensive effort in developing anti-Ras inhibitors for cancer treatment. Despite intensive effort, to date, no effective anti-Ras strategies have successfully made it to the clinic. We present an overview of past and ongoing strategies to inhibit oncogenic Ras in cancer. Since approaches to directly target mutant Ras have not been successful, most efforts have focused on indirect approaches to block Ras membrane association or downstream effector signaling. While inhibitors of effector signaling are currently under clinical evaluation, genome-wide unbiased genetic screens have identified novel directions for future anti-Ras drug discovery.
RAS 癌基因（HRAS、NRAS 和 KRAS）构成了人类癌症中最常突变的致癌基因类别（33%），因此激发了开发抗 Ras 抑制剂用于癌症治疗的巨大努力。尽管付出了巨大努力，但迄今为止，还没有有效的抗 Ras 策略成功进入临床。我们介绍了过去和正在进行的抑制癌症中致癌 Ras 的策略概述。由于直接针对突变 Ras 的方法尚未成功，因此大多数努力都集中在间接方法上，以阻断 Ras 膜结合或下游效应子信号。虽然效应子信号抑制剂目前正在临床评估中，但全基因组无偏遗传筛选已经为未来的抗 Ras 药物发现确定了新的方向。
