Karlic Heidrun, Herrmann Harald, Schulenburg Axel, Grunt Thomas W, Laffer Sylvia, Mirkina Irina, Hubmann Rainer, Shehata Medhat, Marian Brigitte, Selzer Edgar, Pfeilstöcker Michael, Pittermann Elisabeth, Jäger Ulrich, Pehamberger Hubert, Zielinski Christoph, Valent Peter
Ludwig Boltzmann Cluster Oncology (LBI for Leukemia Research), Hanusch Hospital, Vienna, Austria.
Wien Klin Wochenschr. 2010 Jul;122(13-14):423-36. doi: 10.1007/s00508-010-1408-z. Epub 2010 Jul 22.
Biological features of tumor cells relevant to progression, metastasis, and prognosis in cancer patients have been investigated for many years. During the past few years, the concept of tumor stem cells has gained widespread acceptance. The cancer stem cell (CSC) model is based on the observation that continuous growth of tumors depends on a small population of immature neoplastic cells with unlimited proliferative potential. In contrast to these CSC, more mature clonal cells in the same neoplasm undergo apoptosis and die after a variable number of cell divisions. The self-renewal capacity of CSC plays a central role in this scenario and enables permanent tumor cell repopulation in vivo in patients as well as in experimental animals, e.g., immunodeficient mice. Based on the stem cell concept, it is clear that the success of an anti-neoplastic approach depends on efficient targeting and elimination of CSC. An important aspect of CSC is their intrinsic resistance against conventional drugs. Therefore, a major focus in current research is molecular targets and their expression in CSC, with the goal to use targeted drugs for CSC elimination. It is the hope for the future that therapeutic approaches involving CSC-targeting concepts will lead to sustained remission and thus improvement of prognosis in leukemia and cancer patients.
多年来,人们一直在研究肿瘤细胞与癌症患者病情进展、转移及预后相关的生物学特性。在过去几年中,肿瘤干细胞的概念已被广泛接受。癌症干细胞(CSC)模型基于这样的观察结果:肿瘤的持续生长依赖于一小部分具有无限增殖潜能的未成熟肿瘤细胞。与这些CSC相反,同一肿瘤中更成熟的克隆细胞在经历不同次数的细胞分裂后会发生凋亡并死亡。CSC的自我更新能力在这种情况下起着核心作用,并能使患者体内以及实验动物(如免疫缺陷小鼠)体内的肿瘤细胞永久重新增殖。基于干细胞概念,很明显抗肿瘤方法的成功取决于对CSC的有效靶向和清除。CSC的一个重要方面是它们对传统药物的内在抗性。因此,当前研究的一个主要重点是分子靶点及其在CSC中的表达,目标是使用靶向药物清除CSC。未来的希望是,涉及CSC靶向概念的治疗方法将导致持续缓解,从而改善白血病和癌症患者的预后。