Department of Pathology, Yale University School of Medicine, USA.
Anticancer Drugs. 2011 Jun;22(5):384-91. doi: 10.1097/CAD.0b013e3283439781.
Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene are a well-described mechanism of resistance to monoclonal antibodies that target the epidermal growth factor receptor in patients with metastatic and nonoperable colorectal cancer. Treatment options in this population are limited to conventional chemotherapy regimens and antiangiogenesis compounds. Numerous strategies have been proposed in preclinical models as being effective in the presence of KRAS mutations. As basic and translational research further unravels the complex interactions and regulation points in the pathways downstream of epidermal growth factor receptor, more drugs become available for clinical testing. Indeed, there are many ongoing clinical trials that focus on the safety and efficacy of novel compounds in patients with KRAS-mutated colorectal cancer. This is a review of the literature with regard to the rationale of various approaches on this topic and also a summary of the current active clinical trials limited to patients with KRAS-mutated colorectal cancer.
KRAS 基因突变是转移性和不可手术的结直肠癌患者对针对表皮生长因子受体的单克隆抗体产生耐药性的一种已知机制。在这部分人群中，治疗方案仅限于常规化疗方案和抗血管生成药物。在临床前模型中提出了许多策略，这些策略在存在 KRAS 突变的情况下被证明是有效的。随着基础和转化研究进一步揭示表皮生长因子受体下游途径的复杂相互作用和调节点，更多的药物可供临床测试。事实上，有许多正在进行的临床试验专注于新型化合物在 KRAS 突变型结直肠癌患者中的安全性和疗效。这是对该主题各种方法的基本原理的文献综述，也是对目前仅限于 KRAS 突变型结直肠癌患者的活跃临床试验的总结。
