One group of representative targeted oncogenic kinases,the receptor tyrosine

kinases(RTKs),has been associated with gastric cancer development.Trastuzumab,an inhibitor of ERBB2,has been approved for the treatment of gastric cancer,although other receptor tyrosine kinases,such as epidermal growth factor receptor,vascular endothelial growth factor,platelet-derived growth factor receptor,c-Met,IGF-1R and fibroblast growth factor receptor 2,are also activated in gastric cancer.The promising 此网站 results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients.On the other hand,the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients;however,a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial.Other clinical trials,especially phaseⅢtrials that have tested drugs targeting

RTKs,such as cetuximab,panitumumab,gefitinib,erlotinib,figitumumab,sorafenib,sunitinib and lapatinib,have shown that these drugs have modest effects OSI-744 against gastric cancer.This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further

improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies.
系统阐述非小细胞肺癌(NSCLC)患者EGFR-TKI耐药的分子机制及目前已知的治疗策略。资料来源于PubMed数据库及万方数据库。选取2005~2013年发表在核心期刊上的关于非小细胞肺癌EGFR-TKI耐药机制或耐药后治疗的文献,综合达成共识的数据资料,得出数据综合的结果和结论:目前已知的EGFR-TKI耐药的分子机制有T790M突变、C-Met基因扩增、BIM多态性缺失、K-ras基因突变、BRAF基因突变、EML4-ALK融合基因突变及转化为小细胞肺癌等,但针对各种耐药机制开发的药物多处于临床前或临床研究阶段,这些药物的研究为实现肺癌个体化治疗提供了可能。
Hsp90作为热休克蛋白家族中的重要一员,是一种对细胞生存所必需的分子伴侣,它发挥着稳定顾客蛋白构象、维持其功能的作用。许多顾客蛋白在肿瘤中处于过度表达或持续激活状态,与肿瘤的发生发展有着密切的关系。因此,Hsp90在近年的研究中倍受关注,已经发展为抗肿瘤治疗的良好靶点,目前已经有多个Hsp90抑制剂进入临床实验。近年随着肿瘤分子生物学的研究,肿瘤分子靶向治疗已取得明显成果,针对多种癌症已获得了多个用于靶向治疗的单克隆抗体或小分子化学物质,如用于治疗某些HER2阳性乳腺癌的曲妥珠单抗、用于治疗NSCLC的吉非替尼等。然而随着这些药物的应用,肿瘤耐药性不可避免的产生。多方面研究表明Hsp90抑制剂会引起与耐药相关的多个分子的降解,提示其在拮抗耐药方面具有重要的意义。本文就Hsp90分子抑制剂在拮抗肿瘤耐药方面的研究进行综述。
1前言一些遗传学确定的癌症依靠单一过度活跃的癌基因来增殖和生存,这种现象称之为”癌基因成瘾(oncogene 寻找更多 addiction)”,如慢性髓细胞性白血病的BCR-ABL融合基因,非小细胞肺癌(non-smallcell lung cancer,NSCLC)的表皮生长因子受体(epidermal growth factor receptor,EGFR)基因的活
1文献来源研究一:Zou HY,Li Q.An orally available small-molecule inhibitor of c-Met,PF-2341066,exhibits cytoreductive antitumor efficacy throughantiproliferative and antiangiogenic mechanisms[J].Cancer Res,2007,67(9):4408-4417.研究二:Tanizaki J,Okamoto I.