Cancer sternness and metastasis: Therapeutic consequences and perspectives
Cancer sternness and metastasis: Therapeutic consequences and perspectives
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DOI：
10.1016/j.ejca.2010.02.030
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发表时间：
2010-05-01
影响因子：
8.4
通讯作者：
Fodde, Riccardo
中科院分区：
文献类型：
--
作者：
Monteiro, Joana;Fodde, Riccardo
癌细胞转移的瞬时和动态性质不能仅仅用原发肿瘤中发生的不可逆遗传变化的渐进积累来解释。细胞在不同细胞身份之间切换的能力，如上皮细胞向间充质细胞（EMT）和间充质细胞向上皮细胞转化（MET），使它们能够对不同的细胞环境做出反应，从而有效地从原发性肿块传播，最终定植在远处器官。这些更具活力的干细胞样癌细胞具有自我更新和去分化/再分化的能力，并最终在远处器官部位重现原发性肿瘤的异质组成。转移的这一动态概念对癌症诊断、诊断学和治疗具有深远的影响。定义干细胞的许多特征，如休眠、主动DNA修复、几种药物转运蛋白的表达和对细胞凋亡的抗性，可能是迁移癌细胞在基于靶向活跃增殖细胞的遗传毒性剂的常规治疗方案中存活的能力的基础。因此，调节自我更新和分化之间的平衡的信号转导途径可能是未来制定量身定制的干预策略的目标。此外，特定的干细胞特征，如迁移到患病区域的能力（向病理性），为开发能够跟踪和递送抗癌化合物到播散性转移性病变的细胞载体开辟了新的途径。(C)2010爱思唯尔有限公司版权所有。
The transient and dynamic nature of cancer cells that underlie metastasis cannot only be explained by the progressive accumulation of irreversible genetic changes occurring in the primary tumour. The capacity of cells to switch between different cellular identities, as in epithelial to mesenchymal (EMT) and mesenchymal to epithelial transitions (MET), allows them to respond to different cellular environments, thus efficiently disseminating from the primary mass to eventually colonise distant organs. These more dynamic stem-like cancer cells are earmarked by the ability to self-renew and de-/re-differentiate, and eventually recapitulate the heterogeneous composition of the primary tumour in a distant organ site. This dynamic concept of metastasis has profound consequences and implications for cancer diagnostics, prognostics and therapy. Many of the characteristics that define stem cells, like dormancy, active DNA repair, the expression of several drug transporters, and resistance to apoptosis may underlie the capacity of migrating cancer cells to survive conventional therapeutic protocols based on genotoxic agents targeting active proliferating cells. Accordingly, signal transduction pathways that regulate the balance between self-renewal and differentiation are likely to represent future targets in the development of tailor-made intervention strategies. Also, specific stem cell features, such as the capacity to migrate to diseased areas (pathotropism), open novel avenues towards the development of cell vehicles capable of tracking and delivering anti-cancer compounds to disseminated metastatic lesions. (C) 2010 Elsevier Ltd. All rights reserved.