Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Stem Cells. 2014 Jun;32(6):1373-9. doi: 10.1002/stem.1678.
Oncogene addiction describes the dependence of some cancers on one or a few genes for their survival. Inhibition of the corresponding oncoproteins can lead to dramatic responses. However, in some cases, such as chronic myeloid leukemia (CML), a disease characterized by the presence of the abnormal fusion tyrosine kinase BCR-ABL, cancer stem cells may never acquire addiction to the oncogene that drives disease development. The suggested mechanism(s) for treatment failure include a quiescent stem cell population capable of reinstating disease, high levels of oncoprotein expression, or acquired mutations in the oncogene. In this review, we discuss the evidence for oncogene addiction in several solid tumors and their potential escape mechanism(s) with a particular focus on CML stem cells.
癌基因成瘾描述了某些癌症对一种或几种基因的生存依赖。抑制相应的癌蛋白可以导致显著的反应。然而，在某些情况下，如慢性髓性白血病 (CML)，一种以异常融合酪氨酸激酶 BCR-ABL 存在为特征的疾病，癌症干细胞可能永远不会对驱动疾病发展的癌基因产生成瘾。治疗失败的建议机制包括能够重新引发疾病的静止干细胞群体、癌蛋白表达水平高，或癌基因获得突变。在这篇综述中，我们讨论了几种实体瘤中癌基因成瘾的证据及其潜在的逃逸机制，特别关注 CML 干细胞。
