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02/12/07 -- In a new report in the February 15th issue of G&D, Dr. Martin McMahon (UCSF) and colleagues present a novel mouse model of non-small cell lung cancer, which will serve as a useful tool to test the efficacy of novel chemotherapeutic drug therapies in the early stages of lung tumorigenesis. Their paper provides evidence to support the use of a relatively new class of drugs, called MEK inhibitors, for lung cancer patients whose tumors contain mutations in the BRaf gene.
BRaf is one of three members of the RAF kinase family, which, upon activation, induces the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) cell signaling pathway and promotes cell proliferation. Activating mutations in BRaf (ie., a mutation that causes the activation of the catalytic activity of the BRaf protein) are implicated in a number of different human cancers, including the majority of melanoma cancers, as well as in colorectal, thyroid, ovarian and non-small cell lung cancers.
Dr. McMahon and colleagues engineered a strain of mice to carry a version of the BRaf gene that the researchers could activate at will - both temporally and spatially. After activating BRaf specifically in the lungs of mice at 6-8 weeks of age, the researchers observed that the BRaf-mutant mice (or BRaf(VE), as they are known) developed multiple lung tumors that were pathologically similar to human lung tumors - thereby establishing BRaf as a bona fide oncoprotein.
Administration of the MEK-inhibitor, PD0325901 (developed by Pfizer, and now in clinical trials) effectively halted tumor progression in BRaf(VE) mice. Interestingly, however, without pharmacological intervention, the BRaf-mutant tumors eventually stopped proliferating, and entered into a senescent state. This senescent state could be overcome by concomitant mutation of either p53 or p16(Ink4a)/p19(Arf), enabling tumors to become adenocarcinomas.
Dr. McMahon said that the striking response of BRaf(VE)-induced lung tumors to MEK inhibition is most likely because the tumors are at such an early stage of their development. Such observations further emphasize the need for early detection in human lung cancer, since the earlier a tumor is detected the more likely it is to be curable. However, MEK inhibitors may still be useful for late stage cancers, especially if used in conjunction with conventional chemotherapy, a question that McMahon and colleagues are planning to address in their next round of experiments.
Source: Cold Spring Harbor Laboratory
http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=26100026 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Modeling Lung Cancer
肺癌模型
02/12/07 -- In a new report in the February 15th issue of G&D, Dr. Martin McMahon (UCSF) and colleagues present a novel mouse model of non-small cell lung cancer, which will serve as a useful tool to test the efficacy of novel chemotherapeutic drug therapies in the early stages of lung tumorigenesis. Their paper provides evidence to support the use of a relatively new class of drugs, called MEK inhibitors, for lung cancer patients whose tumors contain mutations in the BRaf gene.
将在2月15日冷泉港的G&D（Gene & Development）杂志上刊出的一篇新的报告里，美国加利福尼亚大学旧金山分校的Martin McMahon博士和他的同事们建立了一个新的非小细胞肺癌的小鼠模型，这个模型可以作为有用的工具来测试新的化学药物治疗在肺部肿瘤发生的早期阶段效应。他们的文章为一类称为MEK抑制剂的较新的一类药物的使用提供了证据，肺癌病人的肿瘤包含BRAF致癌基因突变。
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BRaf is one of three members of the RAF kinase family, which, upon activation, induces the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) cell signaling pathway and promotes cell proliferation. Activating mutations in BRaf (ie., a mutation that causes the activation of the catalytic activity of the BRaf protein) are implicated in a number of different human cancers, including the majority of melanoma cancers, as well as in colorectal, thyroid, ovarian and non-small cell lung cancers.
Braf是RAF激酶家族的三个成员之一，.经活化可诱导丝裂原活化蛋白和细胞外信号调节激酶（MEK）细胞信号传导通路以及促进细胞增殖。激活BRAF致癌基因突变（这种突变导致Braf蛋白催化活性激活）与许多不同的人类癌症有关，除了结肠直肠、甲状腺、卵巢及非小细胞肺癌外，还包括大多数黑色素瘤。
Dr. McMahon and colleagues engineered a strain of mice to carry a version of the BRaf gene that the researchers could activate at will - both temporally and spatially. After activating BRaf specifically in the lungs of mice at 6-8 weeks of age, the researchers observed that the BRaf-mutant mice (or BRaf(VE), as they are known) developed multiple lung tumors that were pathologically similar to human lung tumors - thereby establishing BRaf as a bona fide oncoprotein.
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作者:admin@医学,生命科学 2011-02-16 05:12
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