Science Signaling:美研究绘制癌症耐药路径图

2015-01-04 何嫱 生物通

由美国杜克大学癌症研究所领导的一个研究小组,鉴别出了促使某些癌细胞对致命疗法产生耐药的一些关键事件。通过绘制出黑色素瘤细胞、乳腺癌细胞和称作为骨髓纤维化(Myelofibrosis)的一种血癌类型的细胞对某些药物产生耐药的具体步骤,研究人员现在获得了一些靶向这些信号通路,并可维持当前治疗效应的更好的靶点。 两篇研究论文被选作封面故事发表在12月23日的《科学信号》(Science Si

由美国杜克大学癌症研究所领导的一个研究小组,鉴别出了促使某些癌细胞对致命疗法产生耐药的一些关键事件。通过绘制出黑色素瘤细胞、乳腺癌细胞和称作为骨髓纤维化(Myelofibrosis)的一种血癌类型的细胞对某些药物产生耐药的具体步骤,研究人员现在获得了一些靶向这些信号通路,并可维持当前治疗效应的更好的靶点。

两篇研究论文被选作封面故事发表在12月23日的《科学信号》(Science Signaling)杂志上。

论文主要作者、杜克大学药理学及癌症生物学助理教授Kris Wood博士说:“对抗癌治疗产生临床耐药是一个重大问题。要解决这一问题最合理的途径就是了解肿瘤细胞对药物产生耐药的原因,由此开发出一些策略来阻止这些过程。”

“在新研究中,我们开发出了一种筛查技术使得我们能够快速确定细胞可以利用来产生耐药的路径,借助这一信息我们证实了在实验室中看到的这些机制确实也发生于患者的肿瘤之中,”Wood说。

Wood和同事们对一些已知激活时,有潜力引发耐药的细胞信号通路展开了广泛调查。利用这一筛查技术,他们确证了早先一些耐药研究的结果,并发现了从前没有描述过的一些新信号通路。

他们在实验室中鉴别的一些新机制也与临床有关联,其出现在了对治疗产生耐药的患者肿瘤细胞中。

Wood 说:“有趣的是,在三种癌症类型中这些机制非常相似。我们的研究结果表明,在乳腺癌和黑色素瘤中相同的Notch-1信号通路是对一系列广泛靶向治疗产生抵抗的一个潜在驱动因子——过去人们尚未普遍认识到这一作用。”

Wood说,在骨髓纤维化中,研究人员追踪了重要信号分子RAS下游的一对独立信号通路。当这些信号通路激活时,会通过抑制细胞死亡促成对当前的一些标准靶向药物产生耐药。在第二篇Science Signaling论文中,研究人员提出,靶向RAS下游的这些信号通路或许可以维持当前治疗的疗效。

“综上所述,这些研究结果提高了我们将患者进行分类的能力:由此确定哪些更有可能对治疗产生反应,哪些人可能性则较小,并将推动我们设计出一些药物组合来协同作用阻止或延缓耐药,”Wood说。

原始出处:


Martz CA1, Ottina KA2, Singleton KR1, Jasper JS1, Wardell SE1, Peraza-Penton A1, Anderson GR1, Winter PS1, Wang T3, Alley HM1, Kwong LN4, Cooper ZA4, Tetzlaff M4, Chen PL4, Rathmell JC1, Flaherty KT5, Wargo JA4, McDonnell DP1, Sabatini DM6, Wood KC7.Systematic identification of signaling pathways with potential to confer anticancer drug resistance.Sci Signal. 2014 Dec 23;7(357):ra121. doi: 10.1126/scisignal.aaa1877.

P. S. Winter, K. A. Sarosiek, K. H. Lin, M. Meggendorfer, S. Schnittger, A. Letai, K. C. Wood.RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis. Science Signaling, 2014; 7 (357): ra122 DOI: 10.1126/scisignal.2005301

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    2015-12-17 楚秀娟
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    2015-09-10 yaanren
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    2015-01-06 jichang

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