肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)能选择性地诱导肿瘤细胞凋亡,因此作为抗肿瘤药物备受瞩目,现已进入II期临床试验,尽管有报道称部分肿瘤细胞对TRAIL耐药,导致治疗效果不如预期,但TRAIL用于肿瘤治疗的前景依旧被人们看好。通过对TRAIL耐药机理的研究将有助于寻找逆转肿瘤细胞耐药的靶点,并通过联合用药来调节相关的信号分子以获得更好的抗肿瘤效应。该文将介绍TRAIL及其介导的细胞凋亡通路并总结近年来TRAIL耐药机理及逆转其耐药方面的研究进展。
摘要
热休克蛋白作为细胞抵抗外界刺激的产物,能够快速清除异常或变性蛋白而保护细胞免受损伤。近年来研究发现肿瘤细胞中热休克蛋白的水平高于正常细胞,过度表达的热休克蛋白在肿瘤的发生发展过程中起重要作用,且影响肿瘤的治疗效果。本文概述了热休克蛋白与肺癌相关性的研究,总结用于肺癌治疗的热休克蛋白抑制剂的研究现状,并探讨了从中药中筛选高效低毒热休克蛋白抑制剂的可行性,为研究肺癌发病机理及开发高效肺癌药物提供相关参考。
AXL是酪氨酸激酶受体之一,在恶性肿瘤细胞中高表达,并通过多种信号传导途径,尤其是与EMT形成正向反馈循环,促进肿瘤转移和耐药,成为肿瘤治疗的一个新靶点。通过抑制AXL的表达可有效逆转EMT和肿瘤转移与耐药。
胃癌是发病率较高的恶性肿瘤,也是导致肿瘤相关死亡的主要病种。胃癌患者中将近20%HER-2表达阳性。HER-2在HER/erb

Apoptosis抑制剂 B家族的活化和信号转导中起着重要的作用,参与了肿瘤细胞的增殖、分化、转移和细胞转化,HER-2过表达还与鲍曼分型,淋巴转移,静脉浸润,淋巴管浸润相关,HER-2过表达患者预后往往较差。目前针对HER-2靶向治疗的方法包括单克隆抗体、小分子酪氨酸激酶抑制剂等,都取得了一定的疗效,但同时也出现许多新问题有待解决。
Heat shock protein 90(hsp90) is a promising anticancer drug target. A library of 2,4-dihydroxyphenyl(resorcinol) substituted 4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine

compounds that target this protein were designed and prepared based on our earlier study. The compounds were tested in five cancer cell lines and seven of them showed notable anticancer activity(IC_(50)2–10 mmol/L). The active subset compounds were further subjected to a polarized fluorescent assay and exhibited high binding affinity toward purified hsp90(IC_(50)60–100 nmol/L). These results indicated that the tetrahydrotriazolopyrazine motif of the molecules may represent a novel scaffold for the development JNJ-38877605研究购买 of hsp90 inhibitors.
肺癌恶性程度高,是目前发病率和死亡率居首位的恶性肿瘤,其中非小细胞肺癌约占肺癌的80%~85%,且多数患者在确诊时已属晚期。随着对肿瘤发病机制及其生物学行为研究的不断深入,以特异性高、不良反应轻为特点的分子靶向治疗成为目前关注的焦点,如针对EGFR、KRAS及EML4-ALK融合基因等常见突变基因的靶向治疗。但是由于基因检测技术、组织标本获取困难等多种原因,致使大约70%以上的晚期非小细胞肺癌患者不能够接受基因靶向治疗,本文就晚期非小细胞肺癌靶向治疗进行综述。
Despite

improvements in adjuvant therapies for gastric cancer in recent years, the disease is characterized by high recurrence rates and a dismal prognosis. The major improvement in the treatment of recurrent or metastatic Selleck OSI-744 gastric cancer in recent years has been the incorporation of trastuzumab, a monoclonal antibody that inhibits human epidermal growth factor receptor 2(HER2) heterodimerization, after the demonstrated predictive value of the overexpression and/or amplification of this receptor. Beyond HER2, other genetic abnormalities have been identified, and these mutations may be targetable by tyrosine kinase inhibitors or monoclonal antibodies. The demonstration of four distinct molecular subtypes of gastric cancer by the Cancer Genome Atlas study highlight the enormous heterogeneity of the disease and its complex interplay between genetic and epigenetic alterations and provide a roadmap to implement genome-guided personalized therapy in gastric cancer.