Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?
Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?
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DOI：
10.18632/oncotarget.5800
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Tricot G
中科院分区：
文献类型：
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作者：
Franqui-Machin R;Wendlandt EB;Janz S;Zhan F;Tricot G
多发性骨髓瘤（MM）仍然是一种基本上无法治愈的遗传异质性浆细胞恶性肿瘤，与许多其他癌症一样，它含有一小部分克隆性干细胞样细胞，这些细胞表现出明显的自我更新和分化能力，但也表现出明显的耐药性。这些MM干细胞（MMSC）在骨髓瘤研究中是一个有争议但非常重要的问题，因为在我们看来，它们是抗肿瘤化疗将骨髓瘤转化为可管理的慢性疾病失败的根源。包括CD 138-、ALDH 1+和SP在内的几种标记物已被用于鉴定MMSC;然而，没有一种标记物可用于MMSC的分离。尽管如此，现在已知MMSC依赖于自我更新和促生存途径，如AKT、Wnt/β-catenin、Notch和Hedgehog，这些途径可以用在临床前和临床试验中显示出前景的新型药物靶向。在这里，我们回顾了骨髓瘤“干性”的途径，与骨髓微环境的相互作用，促进耐药性，以及必须克服的障碍，以消除MMSC，使骨髓瘤可治愈的疾病。
Multiple myeloma (MM) remains a largely incurable, genetically heterogeneous plasma-cell malignancy that contains – just like many other cancers – a small fraction of clonogenic stem cell-like cells that exhibit pronounced self-renewal and differentiation capacities, but also pronounced drug resistance. These MM stem cells (MMSCs) are a controversial but highly significant issue in myeloma research because, in our opinion, they are at the root of the failure of anti-neoplastic chemotherapies to transform myeloma to a manageable chronic disease. Several markers including CD138−, ALDH1+ and SP have been used to identify MMSCs; however, no single marker is reliable for the isolation of MMSC. Nonetheless, it is now known that MMSCs depend on self-renewal and pro-survival pathways, such as AKT, Wnt/β-catenin, Notch and Hedgehog, which can be targeted with novel drugs that have shown promise in pre-clinical and clinical trials. Here, we review the pathways of myeloma “stemness”, the interactions with the bone marrow microenvironment that promote drug resistance, and the obstacles that must be overcome to eradicate MMSCs and make myeloma a curable disease.