Blagosklonny Mikhail V
Cancer Center, Ordway Research Institute, 150 New Scotland Ave., Albany, New York 12208, USA.
Cancer Biol Ther. 2007 Nov;6(11):1684-90. doi: 10.4161/cbt.6.11.5167. Epub 2007 Oct 10.
It has become a cliché that cancer therapy fails because it does not target rare cancer stem cells (CSCs). Here we are discuss that this is not how therapy fails and not any cancer cell with stem-like properties is CSC. Paradoxically, CSCs must be resting to explain their resistance to therapy yet must be cycling to explain their persistence in cell culture. To solve contradictions, this article introduces the term cancer stemloids (or stem cell-like cells) to describe proliferating self-renewing cells. The stem cell hierarchy (stem--proliferating--terminal cells) exists exactly to separate self-renewal (immortality) from proliferation. Cancer stemloids break the stem cell hierarchy and eventually may replace other cells. While CSC is shielded from any selective pressure and therefore unable to drive tumor progression, cancer stemloids undergo clonal selection, accumulate mutations, thus determining tumor progression and therapeutic failures. Unlike CSC, cancer stemloids are a crucial target for cancer therapy, exactly because they proliferate. Furthermore, two normally mutually-exclusive properties (proliferation and stemness) provide a means to design therapy to kill cancer stemloids selectively without killing normal stem and non-stem cells. In contrast, true CSCs are not only a difficult, but also an insufficient and perhaps even an unnecessary therapeutic target, especially in advanced malignancies.
癌症治疗失败是因为未靶向罕见的癌症干细胞（CSCs），这已成为老生常谈。在此我们讨论的是，治疗失败并非如此，且并非任何具有干细胞样特性的癌细胞都是CSC。矛盾的是，CSCs必须处于静止状态才能解释其对治疗的抗性，但又必须处于循环状态才能解释其在细胞培养中的持久性。为了解决这些矛盾，本文引入了癌症类干细胞（或干细胞样细胞）这一术语来描述增殖性自我更新细胞。干细胞层级结构（干细胞 - 增殖细胞 - 终末细胞）的存在正是为了将自我更新（永生）与增殖区分开来。癌症类干细胞打破了干细胞层级结构，最终可能取代其他细胞。虽然CSC免受任何选择压力，因此无法驱动肿瘤进展，但癌症类干细胞会经历克隆选择，积累突变，从而决定肿瘤进展和治疗失败。与CSC不同，癌症类干细胞正是因为增殖而成为癌症治疗的关键靶点。此外，两种通常相互排斥的特性（增殖和干性）提供了一种设计疗法的方法，可选择性地杀死癌症类干细胞而不杀死正常干细胞和非干细胞。相比之下，真正的CSCs不仅是一个困难的治疗靶点，而且是一个不充分甚至可能不必要的治疗靶点，尤其是在晚期恶性肿瘤中。
