K-Ras基因型对抗肿瘤药物临床疗效预测作用的研究进展

K-Ras蛋白是细胞膜表面的小G蛋白,能将胞外信号通过一系列信号通路转导到细胞内,参与调控细胞的生存、分化和增殖.当K-Ras的基因发生突变时,持续活化的K-Ras导致下游信号的过度激活,进而促进细胞恶性转化和抗肿瘤药物的耐药.各类型肿瘤中存在K-Ras突变的比例超过20％,在胰腺癌中高达61％.用药方案和肿瘤类型的不同,K-Ras基因突变与抗肿瘤药物临床药效之间的关系尚存在一定的争议.本文系统综述了在各类肿瘤中K-Ras基因突变与细胞毒类化疗药物、表皮生长因子受体（Epidermal growth factor receptor,EGFR）单克隆抗体及EGFR酪氨酸激酶抑制药临床疗效关系的研究进展,为K-Ras突变的肿瘤患者的临床个体化用药提供参考.

Research Progress in Predictive Role of K-Ras Mutation in Clinical Efficacy of Anticancer Drugs

ABSTRACTK-Ras protein is a small membrane localized GTPase, which acts as a molecular switch in the cell signaling pathway and involves in the regulation of cell survival, growth and differentiation. The activating K-Ras mutation will up regulate the downstream signals which modulate tumor growth and drug resistance. K-Ras mutation is quite regular in most kinds of cancers with the percentage above 20%, even as high as 61% in pancreatic cancer. However, whether K-Ras mutation affects the efficiency of anti cancer drugs is far from conclusive. This paper summarized the recent progress in the predictive role of K-Ras mutation in the clinical efficacy of cytotoxic agents, the epidermal growth factor receptor (EGFR) monoclonal antibody and EGFR tyrosine kinase inhibitor (TKI), which may provide reference for the individual treatment in cancer patients with K-Ras mutation.