Cancer Cell:解析癌症复发的根源

2013-09-12 佚名 生物通

来自Margaret公主癌症中心的临床研究人员发现了,无法治愈的骨髓癌症——多发性骨髓瘤在一种最初有效的治疗控制疾病达数年后仍顽固逃脱的原因。这项研究在线发表在9月9日的《癌细胞》(Cancer cell)杂志上。 课题负责人、Margaret公主癌症中心血液病学家Rodger Tiedemann说:“未成熟祖细胞的固有耐药性是这一疾病复发的根源。 研究表明,主

来自Margaret公主癌症中心的临床研究人员发现了,无法治愈的骨髓癌症——多发性骨髓瘤在一种最初有效的治疗控制疾病达数年后仍顽固逃脱的原因。这项研究在线发表在9月9日的《癌细胞》(Cancer cell)杂志上。【原文下载】

课题负责人、Margaret公主癌症中心血液病学家Rodger Tiedemann说:“未成熟祖细胞的固有耐药性是这一疾病复发的根源。

研究表明,主要治疗方法是利用一种蛋白酶体抑制药物万珂(Velcade)来杀死构成大部分肿瘤的浆细胞,而祖细胞则不受影响。这些祖细胞随后可增殖并成熟重启疾病过程,即便是在看似完全缓解的患者体内。

Tiedemann 博士说:“williamhill asia 的研究发现揭示了一种治愈多发性骨髓瘤的新方法:同时靶向祖细胞和浆细胞。现在williamhill asia 知道了治疗后祖细胞存留并导致了复发,williamhill asia 就可以快速进入到临床试验中,在患者体内检测这一残留病灶,并尝试用新的药物或有可能已经存在的药物来靶向它。

在解决这一治疗失败困境的过程中,研究人员发现了多发性骨髓瘤癌细胞成熟的一个层次,证实骨髓瘤细胞的成熟层次在蛋白酶体抑制剂敏感性中发挥至关重要的作用。明确地表明了,当前的药物研究将焦点放在开发新的蛋白酶体抑制剂上,仅仅靶向这一路线将永远不可能治愈多发性骨髓瘤。

Tiedemann博士说:“如果你将多发性骨髓瘤视作是杂草,那么Velcade这样的蛋白酶体抑制剂就像一个挑剔的山羊只吃地面上成熟的植物,虽然导致了缓解,但由于它没有将根吃掉,因此有一天杂草会重新长出来。”

研究小组最初在多发性骨髓瘤细胞中对7,500个基因进行了高通量筛查检测,确定了药物反应的效应器,随后研究了来自患者的骨髓活检组织进一步理解了他们的结果。通过这一过程确定了两个基因:IRE1和XBP1调节了对于蛋白酶体抑制剂Velcade的反应以及作为治愈障碍的耐药潜在机制。

1961年,James Till和Ernest McCulloch发现了一些能够反复自我更新的细胞(“干细胞”),开启了一个新的科学领域。自那时起这一科学领域在一直在快速地发展,尤其重要的是癌症干细胞研究之父John Dick分别于1994年和2007年在白血病和结肠癌中鉴别出了癌症干细胞。Tiedemann的新研究发现则强调了了解疾病过程中细胞组织情况的临床重要性。

原文下载

Chungyee Leung-Hagesteijn,Natalie Erdmann,Grace Cheung,Jonathan J. Keats,A. Keith Stewart,Donna E. Reece,Kim Chan Chung,and Rodger E. Tiedemann.Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma.Cancer cell September 9, 2013

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    2014-06-30 维他命
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    2014-02-23 hongbochen
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