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首页 » 癌症研究 » Gut:雷帕霉素老药新用 或可抑制胰腺癌的发展

Gut:雷帕霉素老药新用 或可抑制胰腺癌的发展

来源:生物谷 2014-08-05 10:01

2014年8月5日 讯 /生物谷BIOON/ --近日,刊登在国际杂志Gut上的一篇研究论文中,来自英国格拉斯格大学等处的研究人员通过研究发现了一种老药可以新用,即这种老药可以抑制某种胰腺癌的发展并且阻断其扩散。

文章中研究人员用这种老药(雷帕霉素)来治疗患胰腺癌的小鼠,此前临床试验中,当研究者给所有患者服用雷帕霉素时,并没有发现其可以有效抑制胰腺癌的发展,而在这项研究中,研究人员表示,雷帕霉素可以有效治疗因PTEN基因错误而引发的胰腺癌。当给予因PTEN突变而发生胰腺癌的小鼠雷帕霉素之后后,研究者发现雷帕霉素可以有效阻断癌细胞的扩散和发展,在某些小鼠机体中,雷帕霉素甚至可以促进肿瘤死亡。

雷帕霉素可以阻断一种名为哺乳动物雷帕霉素靶点(mTOR)的蛋白质,mTOR可以控制细胞的生长;研究人员表示,因PTEN突变而产生的胰腺肿瘤或许依赖于mTOR而生长;在对人类机体胰腺肿瘤分析后,研究人员发现5个人中就有1人携带有错误的PTEN基因,而依赖于雷帕霉素的疗法或许会给这些风险个体带来福利。

每年在英国大约有8800人被诊断为胰腺癌,在胰腺癌患者中仅有3%的个体的生存期等于或者多于5年;研究者Kat Arney表示,这项研究对于我们理解为何胰腺癌因个体而已提供了基础,而且也为后期开发治疗胰腺癌的新型疗法提供了思路,下一步我们计划投入更多的人力和物力进行相关的研究,来加速揭示胰腺癌发病的生物学机制,并且为改善患者的健康和生活质量带来帮助。(生物谷Bioon.com)

Targeting mTOR dependency in pancreatic cancer

Douglas C Morran1, Jianmin Wu2, Nigel B Jamieson3, Agata Mrowinska1, Gabriela Kalna1, Saadia A Karim1, Amy Y M Au1, Christopher J Scarlett4, David K Chang2,3,5,6,7, Malgorzata Z Pajak1, Australian Pancreatic Cancer Genome Initiative (APGI), Karin A Oien1,8, Colin J McKay3, C Ross Carter3, Gerry Gillen9, Sue Champion10, Sally L Pimlott10, Kurt I Anderson1, T R Jeffry Evans1,8, Sean M Grimmond7,11, Andrew V Biankin2,3,5,6,7, Owen J Sansom1, Jennifer P Morton1

Objective Pancreatic cancer is a leading cause of cancer-related death in the Western world. Current chemotherapy regimens have modest survival benefit. Thus, novel, effective therapies are required for treatment of this disease. Design Activating KRAS mutation almost always drives pancreatic tumour initiation, however, deregulation of other potentially druggable pathways promotes tumour progression. PTEN loss leads to acceleration of KrasG12D-driven pancreatic ductal adenocarcinoma (PDAC) in mice and these tumours have high levels of mammalian target of rapamycin (mTOR) signalling. To test whether these KRAS PTEN pancreatic tumours show mTOR dependence, we compared response to mTOR inhibition in this model, to the response in another established model of pancreatic cancer, KRAS P53. We also assessed whether there was a subset of pancreatic cancer patients who may respond to mTOR inhibition. Results We found that tumours in KRAS PTEN mice exhibit a remarkable dependence on mTOR signalling. In these tumours, mTOR inhibition leads to proliferative arrest and even tumour regression. Further, we could measure response using clinically applicable positron emission tomography imaging. Importantly, pancreatic tumours driven by activated KRAS and mutant p53 did not respond to treatment. In human tumours, approximately 20% of cases demonstrated low PTEN expression and a gene expression signature that overlaps with murine KRAS PTEN tumours. Conclusions KRAS PTEN tumours are uniquely responsive to mTOR inhibition. Targeted anti-mTOR therapies may offer clinical benefit in subsets of human PDAC selected based on genotype, that are dependent on mTOR signalling. Thus, the genetic signatures of human tumours could be used to direct pancreatic cancer treatment in the future.

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