OncoRay National Center for Radiation Research in Oncology, University Hospital/Medical Faculty Carl Gustav Carus, TU Dresden, Germany.
Radiother Oncol. 2013 Sep;108(3):378-87. doi: 10.1016/j.radonc.2013.06.003. Epub 2013 Jul 3.
Tumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies.
肿瘤是异质性的，包含表型和功能不同的肿瘤细胞的动态混合物。试图解释肿瘤内异质性起源的两个概念是癌症干细胞假说和克隆进化模型。随机模型认为肿瘤在生物学上是同质的，肿瘤内的所有癌细胞都具有同等的能力来促进肿瘤生长，这取决于持续的突变和选择压力。相比之下，干细胞模型表明，癌症异质性是由于起源于一小部分癌症干细胞（CSC）的层次结构，CSC 在生物学上与肿瘤的大部分不同，具有自我更新、致瘤和多谱系潜能。尽管这两个假说作为肿瘤异质性的相互排斥的解释已经讨论了很长时间，但它们很容易调和，成为癌症进化和多样性的驱动力。最近发现的癌细胞可塑性和异质性使得 CSC 群体成为一个难以追踪和根除的移动目标。了解癌症治疗过程中调节 CSC 的信号机制对于优化当前的治疗策略是不可或缺的。
