In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase
the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop 因为 resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted 什么 agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.
Hsp90 is a major protein involved in the
stabilization of various proteins in 
cancer cells.The present investigation focused on the molecular docking simulation studies of flavanols as inhibitors of Hsp90 at the high affinity adenosine triphosphate(ATP)binding site and analyzed absorption,distribution,metabolism,excretion Selleck Anti-infection Compound Library and toxicity(ADME-toxicity).The molecular docking analysis revealed that the flavanols showed competitive inhibition with ATP molecule at the active site and enhanced pharmacological parameters.
目的探讨非小细胞肺癌(NSCLC)微管相关蛋白4-间变性淋巴瘤激酶(EML4-ALK)融合基因靶点的小分子抑制剂克唑替尼治疗的最新进展、耐药机制以及耐药后的策略,为临床应用提供参考。方法搜索Pub
Med和EMBase数据库以及中文万方数据库的关于NSCLC中ALK阳性的最近3 a相关文献,了解ALK融合基因及其靶向药物的最新研究进展。结果针对ALK融合基因靶点的小分子抑制剂克唑替尼和一线标准化疗方案治疗ALK阳性晚期NSCLC患者的对比,结果显示有良好的临床疗效及耐受性,但存在克唑替尼的耐药问题。结论EML4-ALK融合基因靶向药物克唑替尼明显改善了NSCLC患者的生存质量以及生存期,但克唑替尼耐药问题有待于更好地解决,使ALK阳性NSCLC患者得到最大的临床受益。
背景与目的热休克蛋白90AB1(heat shock protein 90 k Da alpha,class B member 1,Hsp90AB1)是ATP依赖的高度保守的分子伴侣,在多种肿瘤细胞中过表达。在肿瘤发生发展的信号传导通路中起着重要作用的一些分子,如表皮生长因子受体(epidermal growth factor receptor,EGFR)、人类表皮生长因子受体-2(human epidermal growth factor receptor-2,HER2)等,均是Hsp90AB1的底物蛋白。Hsp90AB1与这些底物蛋白相互作用并参与细胞的多种病理生理过程。本研究通过检测Hsp90AB1在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的蛋白表达情况以初步探讨其临床意义。方法采用组织微阵列和免疫组织化学染色的方法检测Hsp90AB1在213例NSCLC及相应癌旁正常肺组织中的蛋白表达,并分析Hsp90AB1的表达与NSCLC临床病理参数及患者预后的关系。结果 Hsp90AB1在肺癌组织中的表达水平(阳性率54.0%)高于在正常肺组织中的表达水平(阳性率0.0%,P0.