PNAS:科学家们有望开发出根治胰腺癌的新型疗法

2018-02-08 佚名 “细胞”微信号

在很多胰腺癌患者中,只有当癌症进展到晚期阶段才会被诊断发现,目前并没有有效的疗法来治疗胰腺癌,而且在近几十年里,科学界也在治疗该病上也并没有太大的研究进展,同时很不幸的是,胰腺癌的发病患者数量一直在不断增加。近日,一项刊登在国际杂志PNAS上的研究报告中,来自西班牙国立癌症研究中心(Spanish National Cancer Research Centre ,CNIO)的研究人员通过研究发现了

在很多胰腺癌患者中,只有当癌症进展到晚期阶段才会被诊断发现,目前并没有有效的疗法来治疗胰腺癌,而且在近几十年里,科学界也在治疗该病上也并没有太大的研究进展,同时很不幸的是,胰腺癌的发病患者数量一直在不断增加。近日,一项刊登在国际杂志PNAS上的研究报告中,来自西班牙国立癌症研究中心(Spanish National Cancer Research Centre ,CNIO)的研究人员通过研究发现了一种能有效治疗胰腺癌的新型疗法。

研究者表示,胰腺肿瘤具有如此高的侵略性和复杂性,以至于研究人员无法通过不同的来源来尝试攻击肿瘤细胞,这项研究就为科学家们打开了胰腺癌治疗的一扇大门,然而现在考虑该疗法的临床应用或许还为时尚早。

胰腺癌的一个主要特点就是,肿瘤细胞会嵌入到间质中,间质占据了肿瘤量的90%,其似乎能够形成形成一种屏障来保护癌细胞免于抑制剂、化疗和免疫疗法的损伤;大量研究都重点关注肿瘤细胞,然而研究者对形成间质的细胞知之甚少,尽管有些研究发现,间质的某些组分能够促进肿瘤进展。

近来,多个研究小组都试图尝试消除间质中大量的细胞,即癌症相关的成纤维细胞(CAFs),但研究人员得到的结果却与预期相反,他们发现,甚至处于较高的恶性程度,肿瘤依然会持续进展,而研究人员对这一结果的解释就是,某些被淘汰的细胞或许具有一定的抗肿瘤功能。随后研究人员重点研究来鉴别促进肿瘤生长的间质细胞群(基质细胞群),随后他们还想研究发现如何有效逆转这些细胞,而这种策略或许具有一定的创新性,与其替换掉帮助肿瘤进展的间质细胞,还不如选择性地对其重编程。

研究者Magdolna Djurec解释道,目前很多研究人员都想要阐明间质和肿瘤生长之间的关联,他们洗完更能够找到新型治疗手段,当我们看到清除间质细胞时会带来负面作用时,我们就想试图重编程这些间质细胞,这或许是一种创新性的手段。研究者重点对成纤维细胞亚群进行了相关研究,这种细胞在炎症发生过程中扮演着关键角色,首先他们分析了肿瘤间质成纤维细胞中不同程度表达的所有基因的特性(相比健康胰腺组织的成纤维细胞),他们假设这些促进肿瘤生长的基因能够仅在CAFs中高水平表达,而在健康组织的成纤维细胞中并不会表达。

研究结果表明,名为Saag3的基因与癌症相关的成纤维细胞有关,其能帮助肿瘤不断进展,当研究人员从CAFs中消除这些基因时,这些细胞的行为与正常成纤维细胞非常相似,同时这些细胞也会失去帮助肿瘤细胞不断生长进展的能力,随后研究人员就对这些细胞进行重编程操作,失去去除促肿瘤进展的特性。

本文研究或能为研究人员提供一种新型策略,并结合诸如化疗、免疫疗法或抑制剂疗法来有效抵御胰腺癌,未来很多研究人员或许也会尝试重编程间质细胞来替代去除这些细胞;现在考虑这项研究的临床应用还为时过早,但该研究中研究人员发现了一个新的基因靶点,其能帮助科学家们开发新型胰腺癌疗法。

在人类胰腺样本中,研究人员鉴别除了相同的促肿瘤成纤维细胞群体,同时还发现,当SAA1基因(人类版本的Saa3基因)过量表达时就预示着胰腺癌患者的预后表现较差;后期研究人员还将研究CAFs和正常成纤维细胞中其它基因所扮演的潜在角色,从而为后期开发新型胰腺癌疗法提供新的思路。

原始出处:

Djurec M,et al.Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors.Proc Natl Acad Sci U S A. 2018 Jan 19. pii: 201717802.

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    2018-11-22 drwjr
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    2018-04-16 1891f69b63m

    希望

    0

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    2018-02-12 大爰

    学习了谢谢分享!!

    0

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    2018-02-10 hb2008ye
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    2018-02-08 虈亣靌

    不确定性太多.需要努力学习

    0

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